Sixty-six patients scheduled for coronary artery bypass graft and/or valve surgery were recruited in a prospective, randomized study designed to compare the effectiveness of three analgesic regimens for chest drain removal. Patients were randomized to receive 0.1 mg/kg IV morphine, 20 mL of 0.5% bupivacaine infiltrated subcutaneously, or inhaled 50% nitrous oxide in oxygen (Entonox) via a demand valve. We assessed pain by measuring visual analog scale pain scores before and during drain removal. Median (25th, 75th centile) visual analog scale pain scores associated with drain removal in the bupivacaine, Entonox, and morphine groups were 9.5 mm (3, 18 mm), 37.0 mm (13, 56 mm), and 15.0 mm (7, 27 mm), respectively. The pain scores were higher in the Entonox group compared with the bupivacaine group (P=0.005) and the morphine group (P=0.047). Differences between baseline and drain-removal scores were -0.5 mm (-13, 7 mm), +10 mm (1, 29 mm), and -3.0 mm (-11, 12 mm), respectively. There was no difference among groups in arterial blood pressure, heart rate, PaCO2, oxygenation, or sedation. Bupivacaine and morphine, unlike Entonox, produce lower pain scores associated with drain removal.