This randomized, open-label, three-period crossover study compared the single-dose pharmacokinetics of three dose levels of oxycodone in combination with acetaminophen (5 mg/325 mg, 7.5 mg/500 mg, or 10 mg/650 mg) in healthy volunteers. Serial 24-hour blood samples were collectedfrom 23 fasting subjects after drug administration. The individual dose levels were evaluated on 3 different days, which were separated by washout periods of at least 7 days, in each subject. Oxycodone AUC(0-t), AUC(0-infinity), and Cmax were dose dependent, whereas tma and t(1/2) were not. The most frequently reported adverse events were dizziness, nausea, headache, pruritus, and vomiting. Most adverse events were mild, and all were self-limiting. Only dizziness occurred in a dose-related manner. Increasing dose levels of oxycodone/acetaminophen provides proportional increases in oxycodone Cmax and AUC. Adverse events were predictable based on the opioid pharmacologic actions of this agent.