Given the trend toward early discharge of patients after surgery and the inherent adverse effects of opioid analgesics, we compared a new nonsteroidal antiinflammatory drug, ketorolac tromethamine, given intravenously (iv) and then orally, with two commonly prescribed opioid analgesics in ambulatory patients for up to 1 week after surgery. In this study incorporating a double-blind, multi-dose design, 221 patients who had moderate or severe pain after surgery were randomized to one of three treatment groups: group K30 received 30 mg iv ketorolac twice, then 10 mg iv every 30 min as required to control pain, up to six doses, followed by 10 mg oral ketorolac every 4-6 h; group F50 received 50 micrograms iv fentanyl at the same time intervals as in group K30, followed by 60 mg codeine plus 600 mg acetaminophen (C+A) orally every 4-6 h; and group F10 received the same combination as did group F50, but only 10 micrograms fentanyl per dose. Compared with 50 micrograms fentanyl iv, 30 mg iv ketorolac provided delayed but otherwise equivalent analgesic effects and was associated with similar side effects. Compared with C+A, 10 mg oral ketorolac was associated with a lower incidence of nausea and somnolence and earlier return of bowel function but not better pain relief, drug tolerability, quality of life, or psychologic well-being. Ketorolac, when used in an iv and then oral sequence, is a safe and effective analgesic in the ambulatory surgery setting. It has a slower onset than fentanyl, but causes fewer side effects than C+A.