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Background: Women have a higher operative mortality (OM) after coronary artery bypass graft (CABG) surgery than men. Suggested contributing factors have included women's increased age, advanced disease, comorbidities, and smaller body surface area (BSA). It is unclear whether women's increased risk factors fully account for this difference or whether female gender within itself is associated with increased OM. We attempted to determine whether, all other factors being equal, there is a significant difference in OM between men and women undergoing CABG., Methods and Results: We retrospectively reviewed a clinical database of 15,440 patients who underwent CABG at 31 Midwestern hospitals in 1999-2000. Each patient record consisted of >400 data elements. Risk-adjusted mortality rates were computed using a predictive equation derived by stepwise logistic regression. Overall, women were older, had a higher incidence of diabetes and valvular disease, and were more likely to be presenting in shock. The OM for the entire population was 2.88% (women 4.24% versus men 2.23%, P<0.0001). Lower BSA was found to be an independent predictor of increased mortality, and a direct inverse relationship between BSA and OM was noted. After adjusting for all comorbidities including BSA, female gender remained an independent predictor of increased mortality (risk-adjusted OM was 3.81% for women and 2.43% for men). Thus, whereas risk adjustment reduced women's OM from 90% higher than men's to 22% higher, a significant difference remained., Conclusions: In this contemporary data set from 31 Midwestern hospitals, female gender was an independent predictor of perioperative mortality, even after accounting for all comorbidities, including low BSA.