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Little is known about the effect of anesthetic management on long-term outcomes. We designed a prospective observational study of adult patients undergoing major noncardiac surgery with general anesthesia to determine if mortality in the first year after surgery is associated with demographic, preoperative clinical, surgical, or intraoperative variables. One-year mortality was 5.5% in all patients (n = 1064) and 10.3% in patients ≥65 yr old (n = 243). Multivariate Cox Proportional Hazards modeling identified three variables as significant independent predictors of mortality: patient comorbidity (relative risk, 16.116; P < 0.0001), cumulative deep hypnotic time (Bispectral Index® <45) (relative risk = 1.244/h; P = 0.0121) and intraoperative systolic hypotension (relative risk = 1.036/min; P = 0.0125). Death during the first year after surgery is primarily associated with the natural history of preexisting conditions. However, cumulative deep hypnotic time and intraoperative hypotension were also significant, independent predictors of increased mortality. These associations suggest that intraoperative anesthetic management may affect outcomes over longer time periods than previously appreciated.