Tramadol and hydrocodone are both opioids prescribed to treat moderate to severe pain. Both work slightly differently and may cause different side effects.

Tramadol and hydrocodone are two types of potent pain relievers called opioid analgesics. They’re often used to treat moderate to severe pain, such as long-term pain related to cancer or other chronic conditions. They can also treat pain from an injury or surgery. Hydrocodone is intended for severe chronic pain when nonopioid pain relievers, such as ibuprofen and acetaminophen, haven’t helped.

These drugs have a powerful effect on your brain. They’re both highly effective, but they work in different ways. These drugs also come with their own side effects. Here’s what to know about how tramadol and hydrocodone are similar and different.

Both tramadol and hydrocodone attach to receptors in your brain to change your perception of pain. However, tramadol also allows the chemical messengers norepinephrine and serotonin to remain available to your brain for a longer period. It is believed that this helps block pain signals in your spinal cord.


Generic available—Yes

Brand name—ConZip, Ultram

Forms—Immediate-release tablets and extended-release tablets

Strengths—Immediate release: 50 mg; extended release:
100 mg, 150 mg, 200 mg, 300 mg

Unique side effects:

  • flushing
  • congestion
  • sore throat
  • headache
  • itching
  • weakness
  • seizures


Generic available—No

Brand name— Zohydro ER, Hysingla ER

Forms—Extended-release tablets (Immediate-release hydrocodone is only available in combination products in which it’s combined with other drugs.)

Strengths—Extended release: 20–120 mg

Unique side effects:

  • confusion
  • low blood pressure
  • respiratory depression
  • gastric obstruction

Common side effects of both drugs include:

However, tramadol may also cause:

Most of these mild side effects will resolve within a few days.

Serious side effects

More serious side effects of both drugs can include:

  • mood problems
  • hypersensitivity reactions, including swelling of the tongue or throat, trouble breathing, and skin rash

Additionally, tramadol can cause seizures. Hydrocodone can also cause:

Get immediate medical attention or call 911 if you have any serious side effects from either drug.

Risk factors

Certain people may be more at risk of side effects. Side effects of both drugs are more likely or can be more intense if you are a senior. They can also be more intense if you have kidney or liver disease, chronic obstructive pulmonary disease, or other chronic diseases. People with depression who take tramadol may be at increased risk of suicide.

Tell your doctor and pharmacist about all the medications you take. Many drugs can interact. For example, alcohol and certain over-the-counter drugs that cause sleepiness, including cough or cold formulas, can increase the sedating effect of these drugs.

For more information, read the interactions for tramadol and hydrocodone.

Hydrocodone comes with a black box warning about the potential for misuse. According to the Drug Enforcement Administration (DEA), hydrocodone is associated with more misuse than any other opioid.

It is possible to develop a tolerance to either drug, especially if you don’t take it exactly as your doctor prescribes it. Building a tolerance to a drug means that the same dosage no longer achieves the same effect. People who develop a tolerance often take more of the drug than recommended to get the same feeling.

Tolerance can often lead to dependence. You’re more likely to develop dependence on these drugs if you have a history of drug or alcohol misuse. If you feel yourself becoming dependent, contact your doctor right away.

Don’t stop taking the drug, especially if you have taken it for weeks or months. Your doctor will adjust your dosage to slowly taper you off the drug. This helps prevent withdrawal. Tell your doctor right away if you have withdrawal symptoms when you stop taking either of these drugs.

Learn more: What is opiate withdrawal? »

Before your doctor can recommend an opioid, it’s important that you discuss all underlying medical conditions. List all your over-the-counter and prescription medications and supplements. Tell your doctor if you’ve ever had a problem with alcohol or substance misuse.

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