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Interest in comparing hospital surgical quality continues to increase, particularly with respect to examining certain hospital designations such as National Cancer Institute-designated Cancer Centers (NCI-CC). Our objectives were to compare patients, surgical complexity, and risk-adjusted 30-day outcomes following major cancer surgery at NCI-CC versus non-NCI centers.From the American College of Surgeons National Surgical Quality Improvement Program, patients were identified who underwent colorectal, pancreatic, or esophagogastric resection for cancer (2007–2011). Regression methods were used to evaluate characteristics associated with undergoing treatment at NCI-CCs and surgical-complexity–adjusted 30-day morbidity, mortality, and prolonged length-of-stay at NCI-CC versus non-NCI centers.NCI-CCs performed 20.2% of colorectal (10,555/52,265), 53.5% of pancreatic (6335/11,838), and 49.8% of esophagogastric (1596/3208) operations for cancer. NCI-CCs were more likely to treat patients who were younger, white, and with fewer comorbidities, but were more likely to perform more complex procedures including synchronous liver resection (eg, colorectal), adjacent organ resections (rectal cancer), and vascular reconstructions (eg, pancreas) (all P<0.05). NCI-CCs had a lower mortality rate for colorectal surgery only (1.2% vs. 1.9%) and increased rates of superficial surgical site infection (SSI) for colorectal (9.8% vs. 7.1%) and pancreatic (10.7% vs. 8.8%) surgery. No differences existed for the remaining complications by NCI-CC designation status. NCI-CCs were distributed throughout hospital quality rankings for all procedures and complications assessed.NCI-CCs treated younger, healthier patients, but performed more complex procedures. Patients treated at NCI-CCs had a lower risk of mortality for colorectal resection, but morbidity was similar to non-NCI centers. Comparison of cancer surgery hospital quality is feasible and should adjust for differences in patient demographics, comorbidities, and surgical complexity.