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Background and Objectives: The goal of this study was to compare disease-specific risk factors and 30-day outcomes between patients with Crohn's disease (CD) and colon cancer (CC) undergoing right-sided surgical resection., Methods: The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP®) was interrogated to extract all patients ≥18 years undergoing elective right-sided resection for CD versus CC. Independent risk factors for surgical complications were identified through multivariable logistic regression for both groups. In a second step, surgical and medical 30-day morbidity was compared after risk adjustment., Results: The cohort consisted of 17,516 patients, of which 2,899 (16.6%) underwent surgery for CD versus 14,617 (83.4%) for CC. Independent risk factors for surgical complications in patients with CD were male gender, African American race, ASA score (III or IV), active smoking, prolonged surgery, and preoperative anemia. Independent risk factors for surgical complications in the cancer group were age ≥70 years, male gender, ASA score (III or IV), respiratory and cardiovascular comorbidities, and preoperative hypoalbuminemia (<3.5 g/dL). After risk adjustment, surgical complications (OR 1.25, p = 0.002), sepsis (OR 1.64, p = 0.012), and unplanned readmissions (OR 1.39, p = 0.004) were more common in patients with CD. Thirty-day mortality was higher in cancer patients (1.1 vs. 0.1%, p < 0.0001)., Conclusions: Patients with Crohn's disease were more prone to surgical complications and postoperative sepsis compared to the cancer group undergoing the same procedure. Careful evaluation and correction of disease-specific modifiable risk factors of patients with CD and CC, respectively, are important., (© 2021 The Author(s). Published by S. Karger AG, Basel.)