Background: Studies using Medicare data have suggested that African American race is an independent predictor of death after major surgery. We hypothesized that the apparent adverse effect of race on surgical outcomes is due to confounding by comorbidity, not race itself. Methods: We identified all non-Hispanic white and African American general surgery, private sector patients included in the National Surgery Quality Improvement Program (NSQIP) Patient Safety in Surgery Study (2001-2004). Patient characteristics, comorbidities, and postoperative outcomes were collected/analyzed using NSQIP methodology. Characteristics between races were compared using Student t and χ tests. Odds ratios (OR) for 30-day morbidity and mortality were calculated using multivariable logistic regression. Results: We identified 34,141 white and 5068 African American patients. African Americans were younger but more likely to undergo emergency surgery and present with hypertension, dyspnea, diabetes, renal failure, open wounds/infection, or advanced American Society of Anesthesiology class (all P < 0.001). African Americans underwent less complex procedures but had higher unadjusted 30-day morbidity (14.33% vs. 12.35%; P < 0.001) and mortality (2.09% vs. 1.65%; P = 0.02). After controlling for comorbidity, African American race had no independent effect on mortality (OR 0.95, (0.74-1.23)) but was associated with a higher risk of postoperative cardiac arrest (OR 2.49, (1.80-3.45)) and renal insufficiency/failure (OR 1.70 (1.32-2.18)). Conclusion: African American race is associated with greater comorbidity and cardiac/renal complications but is not an independent predictor of perioperative mortality after general surgery. Efforts to improve postoperative outcomes in African Americans should focus on reducing the need for emergency surgery and improving perioperative management of comorbid conditions.