In their first year of postgraduate training, interns commonly work shifts that are longer than 24 hours. Extended-duration work shifts are associated with increased risks of automobile crash, particularly during a commute from work. Interns may be at risk for other occupation-related injuries. To assess the relationship between extended work duration and rates of percutaneous injuries in a diverse population of interns in the United States. National prospective cohort study of 2737 of the estimated 18,447 interns in US postgraduate residency programs from July 2002 through May 2003. Each month, comprehensive Web-based surveys that asked about work schedules and the occurrence of percutaneous injuries in the previous month were sent to all participants. Case-crossover within-subjects analyses were performed. Comparisons of rates of percutaneous injuries during day work (6:30 am to 5:30 pm) after working overnight (extended work) vs day work that was not preceded by working overnight (nonextended work). We also compared injuries during the nighttime (11:30 pm to 7:30 am) vs the daytime (7:30 am to 3:30 pm). From a total of 17,003 monthly surveys, 498 percutaneous injuries were reported (0.029/intern-month). In 448 injuries, at least 1 contributing factor was reported. Lapse in concentration and fatigue were the 2 most commonly reported contributing factors (64% and 31% of injuries, respectively). Percutaneous injuries were more frequent during extended work compared with nonextended work (1.31/1000 opportunities vs 0.76/1000 opportunities, respectively; odds ratio [OR], 1.61; 95% confidence interval [CI], 1.46-1.78). Extended work injuries occurred after a mean of 29.1 consecutive work hours; nonextended work injuries occurred after a mean of 6.1 consecutive work hours. Injuries were more frequent during the nighttime than during the daytime (1.48/1000 opportunities vs 0.70/1000 opportunities, respectively; OR, 2.04; 95% CI, 1.98-2.11). Extended work duration and night work were associated with an increased risk of percutaneous injuries in this study population of physicians during their first year of clinical training.