Background: Bleeding and need for red blood cell transfusions (RBCT) remain a significant conce with hepatectomy. RBCT carry risk of transfusion-related immunomodulation that may impact post-operative recovery. This study soughs to assess the association between RBCT and post-hepatectomy morbidity. Methods: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) registry, we identified all adult patients undergoing elective hepatectomy over 2007–2012. Two exposure groups were created based on RBCT. Primary outcomes were 30-day major morbidity and mortality. Secondary outcomes included 30-day system-specific morbidity and length of stay (LOS). Relative risks (RR) with 95％ confidence interval (95％ CI) were computed using regression analyses. Sensitivity analyses were conducted to understand how missing data might have impacted the results. Results: A total of 12,180 patients were identified. Of those, 11,712 met inclusion criteria, 2,951 (25.2％) of whom received RBCT. Major morbidity occurred in 14.9％ of patients and was strongly associated with RBCT (25.3％ vs. 11.3％; P<0.001). Transfused patients had higher rates of 30-day mortality (5.6％ vs. 1.0％;P<0.0001). After adjustment for baseline and clinical characteristics, RBCT was independently associated with increased major morbidity (RR 1.80; 95％ CI: 1.61–1.99), mortality (RR 3.62; 95％ CI: 2.68–4.89), and 1.29 times greater LOS (RR 1.29; 95％ CI: 1.25–1.32). Results were robust to a number of sensitivity analyses for missing data. Conclusions: Perioperative RBCT for hepatectomy was independently associated with worse short-term outcomes and prolonged LOS. These findings further the rationale to focus on minimizing RBCT for hepatectomy, when they can be avoided.