Naloxone is an effective opiate antagonist, but its short half-life limits its usefulness. For outpatient procedures, a longer acting opiate antagonist could eliminate two to four hours of nursing observation in patients postoperatively. A controlled, randomized, double-blind trial comparing the effects of nalmefene, naloxone, and placebo in reversing opiate-induced sedation was carried out to determine efficacy, duration of action, and adverse effects in patients undergoing outpatient procedures. Each patient received 1.5 to 3.0 mg/kg meperidine intravenously before the procedure. After the procedure, each patient received either nalmefene, 1.0 mg; naloxone, 1.0 mg; or saline, 1.0 mL intravenously. Vital signs and assessments for alertness were performed for four hours. Naloxone significantly reversed sedation for only 15 minutes, whereas nalmefene was significantly effective (P less than .05) for up to 210 minutes. Nalmefene was significantly more effective than naloxone in reversing sedation at 60, 90, and 120 minutes. Nalmefene is an effective agent for the reversal of opiate-induced sedation after outpatient procedures.