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To determine whether nonemergent major surgery leads to higher mortality when performed on Friday versus early weekdays.Adults admitted emergently to acute-care hospitals on weekends experience higher mortality than those admitted on weekdays.Cohort study of 188,212 patients undergoing nonemergent major surgery at 124 Veterans Affairs hospitals from 2000 to 2004. Risk-adjusted 30-day mortality was compared for operations performed on Fridays versus Mondays through Wednesdays. Data were derived from the Veterans Affairs' National Surgical Quality Improvement Program database. Patients were divided into 3 groups: floor (admitted postoperatively to regular floor), ICU (admitted postoperatively to intensive care unit), and outpatient (not admitted postoperatively). A stepwise logistic regression analysis was used to test the effect of day of surgery (Friday vs. Monday-through-Wednesday) on 30-day mortality in the presence of characteristics that were significant in bivariate analysis.In the floor group (n = 89,786), operations performed on Fridays were associated with a higher 30-day mortality rate than those performed on Mondays through Wednesdays (2.94% vs. 2.18%; odds ratio, 1.36; 95% confidence interval, 1.24–1.49; P < 0.001). After adjusting for patient characteristics, odds ratio of 30-day mortality for operations on Fridays, when compared with Mondays through Wednesdays, was 1.17 (95% confidence interval, 1.05–1.26; P = 0.003). Within the ICU (n = 14,271) and outpatient (n = 84,155) groups, nonsignificant differences in 30-day mortality were observed for operations on Fridays versus Mondays through Wednesdays.For patients admitted to regular hospital floors after nonemergent major surgery, mortality is increased if surgery is performed on Friday versus Monday through Wednesday.