Tramadol and hydrocodone are two types of potent pain relievers called opioid analgesics. Both work slightly differently and may cause different side effects.

Tramadol is a synthetic opioid. Synthetic opioids are lab-made substances designed to mimic the effects of naturally occurring opiates.

Hydrocodone is a semi-synthetic opioid, meaning it was created in a lab using naturally occurring compounds from opium poppies (Papaver somniferum).

The federal government regulates, or controls, opioids. Controlled substances are organized into different categories, called schedules, based on the potential for misuse or dependence.

Drug schedules typically take the form of Roman numerals rather than standard numbers, so you’ll often see them referred to as I, II, III, IV, or V rather than 1, 2, 3, 4, or 5.

Schedule I drugs have the highest potential for misuse and the potential to create severe physical or psychological dependence. Schedule V drugs have the lowest.

The Drug Enforcement Administration (DEA) classifies tramadol as a Schedule IV drug and hydrocodone as a Schedule II drug. This means tramadol is considered less potent than hydrocodone. However, both drugs still have the potential for misuse or dependence.

Hydrocodone and tramadol can be used to treat acute (short-term) pain caused by an injury or surgery. However, doctors usually prescribe them to treat chronic (long-term) pain caused by an underlying condition, like cancer.

Both medications attach to receptors in your brain to change your pain perception.

Tramadol also allows the chemical messengers norepinephrine and serotonin to remain available to your brain for a longer period. This may help block pain signals in your spinal cord.

Doctors usually prescribe opioids as a combination medication containing a simple, non-opioid analgesic. Non-opioid analgesics stop the production of certain chemicals in your brain, which can help relieve pain.

For example, doctors typically prescribe hydrocodone with acetaminophen or ibuprofen, which is a nonsteroidal anti-inflammatory drug (NSAID). Sometimes, doctors may also prescribe it with homatropine to relieve cough and congestion.

Tramadol is usually prescribed with acetaminophen or celecoxib, which is another NSAID.

Opioid analgesics that do not contain other active ingredients may only be prescribed when other pain relievers haven’t worked.

Generic tramadol is available as an immediate-release (IR) or extended-release (ER) oral tablet.

Brand-name versions are also available. ER oral capsules are sold as ConZip, and a liquid solution is sold as Qdolo. The brand Ultram is no longer manufactured.

Hydrocodone is only available as a brand-name ER oral tablet called Hysingla ER. The brand Zohydro ER is no longer manufactured.


  • Generic IR tablets: 25 milligrams (mg), 50 mg, or 100 mg
  • Generic ER tablets: 100 mg, 200 mg, or 300 mg
  • ConZip ER capsules: 100 mg, 200 mg, or 300 mg
  • Qdolo liquid: 5 mg per 1 milliliter (mL)

IR medications are typically taken every 4–6 hours as needed for pain, up to a maximum daily limit of 400 mg. Qdolo liquid may also fall into this category, so confirm with your prescribing doctor.

ER medications are typically taken once per day as part of a consistent pain management protocol.


  • Hysingla ER: 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg, or 120 mg

Hysingla ER is generally taken once per day as part of a consistent pain management protocol.

However, the maximum daily dose varies from person to person. Your prescribing doctor will work with you to develop an appropriate treatment plan.

Take precautions

If you use opioids — of any kind, legal or not — it’s a good idea to have nasal naloxone (Narcan) or injectable naloxone (Zimhi) on hand.

Ensure a trusted person knows where to find your naloxone and how to administer it properly. Administering naloxone can save your life in the event of an unintentional opioid overdose.

Naloxone is available without a prescription in all states, Washington, D.C., and Puerto Rico. If you have insurance coverage, you may be able to get the medication for free.

Many harm reduction programs offer free naloxone. Check out the National Community Based Naloxone Finder Map to find one near you.

Tramadol and hydrocodone are both effective pain relievers. However, research comparing the effects of these medications is somewhat limited.

A double-blind study published in 1998 compared the effects of hydrocodone/acetaminophen and tramadol in 68 people with musculoskeletal pain after a minor traumatic injury.

Each participant took a capsule containing either 5 mg of hydrocodone with 500 mg of acetaminophen or 100 mg of tramadol. Pain levels were evaluated once every 30 minutes over a span of 3 hours using a visual analog scale.

Although the average pain score for both groups was about the same at first, a clear difference in pain became more apparent with each evaluation. Researchers found that hydrocodone/acetaminophen was significantly more effective than tramadol.

A double-blind study published in 2008 compared the effects of hydrocodone/acetaminophen and tramadol in 118 people with chronic cancer pain. Both groups experienced similar levels of pain relief. Tramadol was associated with milder side effects.

More recent research published in 2023 compared the effects of tramadol, oxycodone or hydrocodone, and a combination of tramadol and oxycodone or hydrocodone in 121 people with pain after anterior cruciate ligament (ACL) reconstruction or arthroscopic debridement surgery.

Participants received a daily questionnaire for the first 10 postoperative days. They were asked to self-report:

  • pain at various time points throughout the day
  • total prescription pain medication intake
  • if their pain was not controlled on their regimen
  • if they experienced any side effects
  • if they used supplemental ibuprofen, naproxen, or acetaminophen
  • total over-the-counter pain medication intake

Researchers concluded that tramadol provides similar — and, in most cases, better — pain relief for ACL reconstruction and arthroscopic knee debridement than the other medications studied. Tramadol was also associated with fewer side effects.

Because tramadol and hydrocodone are both opioid drugs, they share similar side effects.

Common side effects can include:

Other side effects of tramadol include:

  • indigestion
  • diarrhea
  • sweating
  • weakness
  • difficulty sleeping

Other side effects of hydrocodone include:

  • stomach pain
  • upper respiratory tract infection
  • acid reflux
  • cough
  • rash
Medical emergency

Call 911 or your local emergency services if you experience any of the following:

  • confusion
  • fever
  • inability to urinate or painful urination
  • muscle stiffness or spasms
  • rapid heart rate
  • seizures
  • shortness of breath or difficulty breathing
  • swelling of your tongue or throat
  • thoughts of suicide

Your doctor will work with you to determine the best medication for your needs and advise you on any side effects or risks associated with use.

Tolerance, dependence, and withdrawal

If you use tramadol or hydrocodone for an extended period of time, your body may develop a tolerance to the drug. You may need a higher dosage to experience the same effects.

Consult your prescribing doctor if you suspect you’ve developed a tolerance. They can review your overall care plan and determine whether it’s appropriate to increase your dose or taper off the medication.

Over time, your body may depend on the drug to function. If you stop taking it, you’ll experience withdrawal symptoms. It’s best to work with a qualified healthcare professional to taper off the medication slowly.

Drug interactions

Opioids can be dangerous when used alongside certain drugs. Opioids interact with:

  • alcohol
  • antiseizure medications
  • benzodiazepines
  • certain antibiotics and antifungal medications
  • certain antidepressants
  • certain HIV medications
  • muscle relaxants
  • sleep medications

It’s important to share your full medication list with your healthcare professional, including:

  • over-the-counter drugs
  • vitamins
  • supplements
  • other substances, including nonprescription drugs

Drug-condition interactions

Your doctor will consider your medical history before prescribing any medication, so tell them about any symptoms, diagnoses, or other changes that aren’t listed in your medical chart.

Tramadol or hydrocodone may worsen the effects of certain underlying conditions, including:

Tramadol and hydrocodone are both prescribed to treat moderate to severe pain.

Doctors usually prescribe them as a combination medication, such as tramadol/acetaminophen, hydrocodone/acetaminophen, or hydrocodone/ibuprofen.

Drugs containing only tramadol or only hydrocodone may be prescribed if other pain relievers haven’t worked.

Discuss the potential benefits, side effects, and risks of these and other opioids with your doctor. Together, you can choose the most effective treatment necessary to relieve your pain.