Nausea and vomiting are common side effects of opioids administered for pain control. This double-blind, randomized, parallel-group study evaluated the anti-emetic efficacy and tolerability of single intravenous (i.v.) doses of ondansetron 8 mg, ondansetron 16 mg and metoclopramide 10 mg in the treatment of opioid-induced emesis. Adult patients undergoing low emetogenic surgical procedures, using a standardized anaesthesia regimen were assessed for 24 h following administration of study anti-emetic to treat established post-surgical opioid-induced emesis. A total of 4511 patients were enrolled of whom 1366 experienced opioid-induced emesis and received randomized study medication. Ondansetron 8 mg and 16 mg were significantly better than metoclopramide 10 mg (P < 0.05) for both complete control of emesis, complete control of nausea and other efficacy measures. There were no significant differences between the two ondansetron groups. All three treatments were well tolerated. In conclusion, this large, multicentre study demonstrates that ondansetron is more effective than metoclopramide in the treatment of opioid-induced emesis following administration of post-surgical opioids to control pain.