Purpose: Oral analgesia after "fast-track" cardiac anesthesia has not been explored. The aim of this study was to compare two oral oxycodone analgesic regimens. Methods: One hundred-twenty patients scheduled for coronary artery bypass grafting were randomly assigned postoperatively to receive immediate-release oxycodone 5 mg and acetaminophen 325 mg (Percocet-5) (group I) per os four times daily, or controlled-release oxycodone 10 mg (OxyContin) (group II) per os every 12 hr and placebo twice daily. Acetaminophen 500 mg per os was used as first-line rescue medication, and immediate-release oxycodone (syrup form) 5 mg per os as second-line rescue medication. Pain intensity was assessed with a visual analogue scale on the first postoperative day, the morning after extubation, and thereafter four times daily for four days. Use of rescue medication and adverse events were recorded. Results: Baseline demographic and operation-related characteristics were similar in both groups. While pain control was good in both groups, the immediate-release group experienced less pain on all postoperative days (P = 0.003), required significantly less rescue medication, and had fewer adverse effects such as somnolence and nausea. Conclusion: Peroral oxycodone is effective for early pain control after fast-track cardiac anesthesia. Immediate-release oxycodone/acetaminophen appears to provide better analgesia and fewer side effects compared to controlled-release oxycodone.