Oxycodone is roughly 1.5 times stronger than hydrocodone, the opioid in Vicodin. Milligram for milligram, 10 mg of oxycodone provides about the same pain relief as 15 mg of hydrocodone. That difference is consistent across both the CDC’s prescribing guidelines and UCSF’s pain management conversion tables, which assign oxycodone a potency factor of 1.5 compared to hydrocodone’s 1.0.
How the Potency Difference Is Measured
Doctors compare opioid strength using a standard called the morphine milligram equivalent, or MME. It converts every opioid to its equivalent dose of oral morphine, creating an apples-to-apples comparison. Hydrocodone has an MME factor of 1.0, meaning it’s essentially equal to morphine milligram for milligram. Oxycodone has an MME factor of 1.5, so each milligram hits about 50% harder than the same milligram of hydrocodone or morphine.
This doesn’t mean oxycodone always produces more pain relief in practice. Prescribed doses are adjusted to account for the potency gap. A doctor prescribing oxycodone will typically use a lower milligram dose than they would with hydrocodone to achieve a similar effect.
What’s Actually in Vicodin vs. Percocet
Vicodin and Percocet are the brand names people usually mean when comparing these two opioids. Both are combination tablets pairing an opioid with acetaminophen (the active ingredient in Tylenol), but they use different opioids.
- Vicodin contains hydrocodone plus acetaminophen. Standard Vicodin has 5 mg of hydrocodone and 300 mg of acetaminophen. Vicodin ES bumps the hydrocodone to 7.5 mg, and Vicodin HP goes up to 10 mg.
- Percocet contains oxycodone plus acetaminophen. It comes in four strengths: 2.5, 5, 7.5, or 10 mg of oxycodone, each paired with 325 mg of acetaminophen.
So a standard Vicodin tablet (5 mg hydrocodone) has an MME of 5, while a standard Percocet tablet (5 mg oxycodone) has an MME of 7.5. That single Percocet is delivering 50% more opioid punch despite the same number on the label.
Does Stronger Mean Better Pain Relief?
Not necessarily. A large randomized trial published in JAMA tested this head-to-head in over 400 emergency department patients with moderate to severe pain from arm or leg injuries. One group received 5 mg oxycodone with 325 mg acetaminophen; another received 5 mg hydrocodone with 300 mg acetaminophen. After two hours, the oxycodone group’s pain scores dropped by 4.4 points on a 10-point scale, while the hydrocodone group dropped by 3.5 points.
That 0.9-point difference sounds meaningful, but pain researchers generally consider 1.3 points the minimum difference a patient can actually feel. The gap between oxycodone and hydrocodone fell below that threshold, meaning most patients couldn’t distinguish one from the other at those doses. Both provided substantial relief.
The takeaway: oxycodone’s higher potency per milligram is real, but when doctors prescribe appropriate doses of either drug, the actual pain relief patients experience is comparable.
How They Work in the Body
Both oxycodone and hydrocodone activate the same primary target in the brain and spinal cord: the mu-opioid receptor. This receptor controls pain signaling, but it’s also responsible for the sedation, euphoria, slowed digestion, and breathing suppression that all opioids share. Neither drug is selective enough to relieve pain without triggering those other effects.
In lab measurements of how tightly each drug binds to that receptor, oxycodone and hydrocodone fall into the same moderate-affinity category, alongside morphine, methadone, and fentanyl. Drugs like codeine and tramadol bind much more loosely, which is one reason they’re considered weaker painkillers. Oxycodone’s slightly higher clinical potency likely comes from differences in how efficiently the body absorbs and processes it rather than a dramatically stronger grip on the receptor itself.
Side Effects Are Similar
Because both drugs work through the same receptor, their side effect profiles overlap almost completely. Constipation is the most common problem with both and tends to persist for as long as you take either medication. Unlike many side effects, the body doesn’t build tolerance to opioid-induced constipation over time.
Nausea, drowsiness, dizziness, and itching are also common with both drugs. The most dangerous side effect, respiratory depression (slow, shallow breathing), applies equally. That risk scales with dose, and because oxycodone is more potent per milligram, taking the same number of milligrams of oxycodone carries a higher overdose risk than the same number of milligrams of hydrocodone. This is why the dose adjustment matters.
Why Doctors Choose One Over the Other
The CDC’s 2022 prescribing guideline doesn’t recommend oxycodone over hydrocodone or vice versa for any specific type of pain. Instead, it emphasizes starting with the lowest effective dose of whichever immediate-release opioid is chosen, using it for the shortest duration necessary, and preferring non-opioid options when possible for ongoing pain.
In practice, the choice often comes down to a patient’s individual response. Some people metabolize one drug more efficiently than the other due to genetic differences in liver enzymes, which can make one feel stronger or cause more side effects. If you’ve taken one and it didn’t work well or caused problems, your doctor may try the other. The two are close enough in clinical performance that switching between them is common and straightforward.
Oxycodone is also available without acetaminophen (as OxyContin in extended-release form, or as immediate-release oxycodone tablets), giving it more prescribing flexibility. Hydrocodone was historically only available combined with acetaminophen, though a standalone extended-release version now exists as well. For people who need to avoid acetaminophen due to liver concerns, this distinction can influence which drug a provider selects.