Background Both anemia and blood transfusion are associated with poor outcomes. The aim of this study was to evaluate the effect of preoperative blood transfusion on postoperative outcomes after colectomy, stratified by severity of anemia. Methods Patients undergoing colectomy from 2012–2014 were selected from the National Surgical Quality Improvement Program targeted colectomy database. Patients were divided into 2 groups based on receipt of preoperative transfusion and then stratified by hematocrit. Univariate and multivariate analyses were used to compare 30-day outcomes between the 2 groups. Results A total of 60,785 patients were included in the study, with an overall preoperative transfusion rate of 3.4% (n = 2,073). On univariate analysis, transfusion was associated with significantly greater rates of postoperative morbidity. The risk-adjusted, multivariate model confirmed increased risk of complications with preoperative transfusion (odds ratio 1.32, 95% confidence interval, 1.18–1.48). Furthermore, transfusion did not improve outcomes even in the setting of moderate anemia (odds ratio 1.35, 95% confidence interval, 1.14–1.60) or severe anemia (odds ratio 0.97, 95% confidence interval, 0.66–1.41). Conclusions Preoperative transfusion is an independent predictor of complications in patients with mild and moderate anemia. Furthermore, these retrospective data suggest that even severely anemic patients do not benefit from preoperative transfusion and empiric transfusion therefore should be avoided. Alternatives to preoperative optimization of this high-risk surgical population should be sought.