BACKGROUND Although nurse staffing has been found to be related to patient mortality, there has been limited study of the independent effect of work schedules on patient care outcomes. OBJECTIVE To determine if, in hospitals where nurses report more adverse work schedules, there would be increased patient mortality, controlling for staffing. METHODS A cross-sectional design was used, with multilevel data from a 2004 survey of 633 nurses working in 71 acute nonfederal hospitals in North Carolina and Illinois. Mortality measures were the risk-adjusted Agency for Healthcare Research and Quality Inpatient Quality Indicators, and staffing data were from the American Hospital Association Annual Survey of hospitals. Principal components analysis was conducted on the 12 work schedule items to create eight independent components. Generalized estimating equations were used to examine the study hypothesis. RESULTS Work schedule was related significantly to mortality when staffing levels and hospital characteristics were controlled. Pneumonia deaths were significantly more likely in hospitals where nurses reported schedules with long work hours (odds ratio [OR] = 1.42, 95% confidence interval [CI] = 1.17-1.73, p < .01) and lack of time away from work (OR = 1.24, 95% CI = 1.03-1.50, p < .05). Abdominal aortic aneurysm was also associated significantly with the lack of time away (OR = 1.39, 95% CI = 1.11-1.73, p < .01). For patients with congestive heart failure, mortality was associated with working while sick (OR = 1.39, 95% CI = 1.13-1.72, p < .01), whereas acute myocardial infarction was associated significantly with weekly burden (hours per week; days in a row) for nurses (OR = 1.33, 95% CI = 1.09-1.63, p < .01). DISCUSSION In addition to staffing, nurses' work schedules are associated with patient mortality. This suggests that work schedule has an independent effect on patient outcomes.