Objective: Melatonin has received considerable publicity for its sleep-promoting properties; however, there is little scientific evidence of its efficacy. The objective of this study is to determine whether there are measurable beneficial effects from exogenous melatonin in emergency physicians after intermittent night-shift duty. Methods: This randomized, placebo-controlled, double-blind, crossover trial was conducted in the emergency department of an urban tertiary care hospital. Fifteen emergency physicians were given melatonin 5 mg or placebo for 3 consecutive nights after night-shift duty with crossover to the opposite agent after a subsequent block of night shifts. The primary outcome measure was the global assessment of recovery measured by a visual analog scale. Secondary outcome measures included sleep quality, duration, and tiredness. In addition, the Profile of Mood States questionnaire and neuropsychologic testing were performed. Results: There was no difference between melatonin and placebo in the global assessment of recovery (60.4±16.9 and 58.9±14.5, respectively; P =.29). There were no differences in sleep quality, duration or tiredness scores, sleep latency, hours of sleep obtained per night, and night or early awakening at any measurement point. Profile of Mood States and neuropsychologic test performances were similar. Conclusion: We found no beneficial effect of melatonin on sleep quality, tiredness, or cognitive function in emergency physicians after night-shift duty. Our results suggest that exogenous melatonin is of limited value in recovery from night-shift work in emergency physicians. [Wright SW, Lawrence LM, Wrenn KD, Haynes ML, Welch LW, Schlack HM: Randomized clinical trial of melatonin after night-shift work: Efficacy and neuropsychologic effects. Ann Emerg Med September 1998;32:334-340.]