Background Prolonged steroid therapy is reportedly associated with changes in coagulation, suggesting increased intraoperative bleeding or hypercoagulability. The aim of this retrospective study was to assess whether long-term steroid use was associated with increased transfusion requirements, infection, or hypercoagulability in adults undergoing noncardiac surgery. Methods In this study the authors evaluated 363,897 patients from the American College of Surgeons National Surgical Quality Improvement Program database. Patients with current pneumonia, ventilator dependence, coma, tumor involving the central nervous system, disseminated cancer, preoperative open wound/wound infection, and/or bleeding disorders were excluded. Each steroid user was matched to a nonsteroid user based on propensity score and type of surgery. Results 296,059 patients met the inclusion criteria, of whom 7,760 (2.6%) were taking steroids preoperatively. The incidence of intraoperative erythrocyte transfusion was 3.6% in the steroid user and 7.3% in non-steroid-user groups. After matching, the mean [95% confidence interval] number of units transfused was 0.22 [0.19, 0.25] units in the nonsteroid group and 0.19 [0.17, 0.22] units in the steroid group which was not statistically significant (P = 0.24, Wald test). Steroid users were 24% [2, 49] more likely to experience 30-day postoperative systemic infection and 21% [3, 41] more likely to experience postoperative wound infection than nonusers. The risks of postoperative thromboembolic complications did not differ significantly. Conclusions The effect of prolonged steroid use on bleeding, if any, thus seems likely to be small and is probably of limited clinical consequence. In contrast, corticosteroid use augments the risk of both systemic and wound infections.