There are no studies evaluating S(+)-ketamine for pain management after sternotomy. In this prospective, randomized, double-blind, placebo-controlled clinical trial, we evaluated the efficacy and feasibility of S(+)-ketamine as an adjunctive analgesic after cardiac surgery. Ninety patients scheduled for elective coronary artery bypass grafting (CABG) were randomized to receive either a 75 microg/kg bolus of S(+)-ketamine followed by a continuous infusion of 1.25 microg . kg(-1) . min(-1) for 48 h (n = 44) or placebo (normal saline bolus and infusion) (n = 46). From the time of tracheal extubation, patients could access an opioid (oxycodone) via a patient-controlled analgesia device, and the cumulative oxycodone doses were measured over 48 h. Pain was evaluated on a visual analog scale three times daily. The quality of recovery, patient satisfaction with pain management, and adverse effects were recorded. The cumulative oxycodone consumption during the first 48 postoperative hours was less in the S(+)-ketamine group (103 +/- 44 mg) than in the placebo group (125 +/- 45 mg; mean difference, 22 mg; 95% confidence interval for the difference, 3-40 mg; P = 0.023). Pain scores did not differ between the groups at rest (P = 0.17) or during a deep breath (P = 0.23). Patient satisfaction was superior in S(+)-ketamine-treated patients: 26 (60%) of 44 in the S(+)-ketamine group compared with 16 (35%) of 46 in the placebo group were very satisfied with the analgesic management (P = 0.032). Nausea and vomiting were the most common adverse events, with similar frequencies in both groups. Four patients in the S(+)-ketamine group developed transient hallucinations during the infusion, versus none in the placebo group. In conclusion, small-dose S(+)-ketamine decreased opioid consumption in CABG patients during the first 48 h after surgery.