Background Evidence supporting worse outcomes among obese patients is inconsistent. This study examined associations between body mass index (BMI) and outcomes after major resection for cancer. Methods Data from the 2005-2012 ACS-NSQIP were used to identify cancer patients (â‰¥ 18 years) undergoing 1 of 6 major resections: lung surgery, esophagectomy, hepatectomy, gastrectomy, colectomy, or pancreatectomy. We used crude and multivariable regression to compare differences in 30-day mortality, serious and overall morbidity, duration of stay, and operative time among 3 BMI cohorts defined by the World Health Organization: normal versus underweight, overweight-obese I, and obese II-III. Propensity-scored secondary assessment and resection type-specific stratified analyses corroborated results. Results A total of 529,955 patients met inclusion criteria; 32.06% had normal BMI, 3.45% were underweight, 32.52% overweight, and 17.76%, 7.51%, and 4.94% obese I-III, respectively. Risk-adjusted outcomes for underweight patients consistently were worse. Overweight-obese I fared similarly to patients with normal BMI but had greater odds of isolated complications. Obese II-III patients experienced only marginally increased odds of morbidity. Analyses among propensity-scored cohorts and stratified by cancer-resection type reported similar trends. Worse outcomes were observed among morbidly obese hepatectomy and pancreatectomy patients. Conclusion Evidence-based assessment of outcomes after major resection for cancer suggests that obese patients should be treated with the aim for optimal oncologic standards without being hindered by a misleading perception of prohibitively increased perioperative risk. Underweight and certain types of morbidly obese patients require targeted provision of appropriate care.