We examine whether a 40-minute nap opportunity at 3 AM can improve cognitive and psychomotor performance in physicians and nurses working 12-hour night shifts. This is a randomized controlled trial of 49 physicians and nurses working 3 consecutive night shifts in an academic emergency department. Subjects were randomized to a control group (no-nap condition=NONE) or nap intervention group (40-minute nap opportunity at 3 AM=NAP). The main outcome measures were Psychomotor Vigilance Task, Probe Recall Memory Task, CathSim intravenous insertion virtual reality simulation, and Profile of Mood States, which were administered before (6:30 PM), during (4 AM), and after (7:30 AM) night shifts. A 40-minute driving simulation was administered at 8 AM and videotaped for behavioral signs of sleepiness and driving accuracy. During the nap period, standard polysomnographic data were recorded. Polysomnographic data revealed that 90% of nap subjects were able to sleep for an average of 24.8 minutes (SD 11.1). At 7:30 AM, the nap group had fewer performance lapses (NAP 3.13, NONE 4.12; p<0.03; mean difference 0.99; 95% CI: -0.1-2.08), reported more vigor (NAP 4.44, NONE 2.39; p<0.03; mean difference 2.05; 95% CI: 0.63-3.47), less fatigue (NAP 7.4, NONE 10.43; p<0.05; mean difference 3.03; 95% CI: 1.11-4.95), and less sleepiness (NAP 5.36, NONE 6.48; p<0.03; mean difference 1.12; 95% CI: 0.41-1.83). They tended to more quickly complete the intravenous insertion (NAP 66.40 sec, NONE 86.48 sec; p=0.10; mean difference 20.08; 95% CI: 4.64-35.52), exhibit less dangerous driving and display fewer behavioral signs of sleepiness during the driving simulation. Immediately after the nap (4 AM), the subjects scored more poorly on Probed Recall Memory (NAP 2.76, NONE 3.7; p<0.05; mean difference 0.94; 95% CI: 0.20-1.68). A nap at 3 AM improved performance and subjective report in physicians and nurses at 7:30 AM compared to a no-nap condition. Immediately after the nap, memory temporarily worsened. The nap group did not perform any better than the no-nap group during a simulated drive home after the night shift.