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To investigate the effect of modafinil 200 mg on the performance of a cohort of healthy male doctors after 1 night of supervised sleep deprivation.Sleep-deprived and fatigued doctors pose a safety risk to themselves and their patients. Yet, because of the around-the-clock nature of medical practice, doctors frequently care for patients after periods of extended wakefulness or during circadian troughs. Studies suggest that a group of substances may be capable of safely and effectively reversing the effects of fatigue. However, little work has been done to investigate their role within our profession.We conducted a parallel, double-blind, randomized, and placebo-controlled study to investigate the effect of pharmacological enhancement on performance doctors. Thirty-nine healthy male resident doctors received either lactose placebo (n = 19) or modafinil 200 mg (n = 20) after 1 night of sleep deprivation. A selection of CANTAB neuropsychological tests was used to assess higher cognitive function. Clinical psychomotor performance was assessed using the Minimally Invasive Surgical Trainer Virtual Reality. Assessments were carried out between 6.00 AM and approximately 8.00 AM.Modafinil improved performance on tests of higher cognitive function; participants in the modafinil group worked more efficiently when solving working memory (F1,38 = 5.24, P = 0.028) and planning (F1,38 = 4.34, P = 0.04) problems, were less-impulsive decision makers (F1,37 = 6.76, P = 0.01), and were more able to flexibly redirect their attention (F1,38 = 4.64, P = 0.038). In contrast, no improvement was seen in tests of clinical psychomotor performance.Our results suggest that fatigued doctors might benefit from pharmacological enhancement in situations that require efficient information processing, flexible thinking, and decision making under time pressure. However, no improvement is likely to be seen in the performance of basic procedural tasks.