BACKGROUND: High-quality surgical resection of colonic cancer, including dissection along the embryologic mesocolic plane, translates into improved long-term oncological outcomes. OBJECTIVE: This study aimed to identify risk factors for compromised specimen quality and to evaluate the specimen quality of patients undergoing laparoscopic and open resection for colonic cancer. DESIGN: This is a retrospective observational study. SETTINGS: This database study is based on the prospective national Danish Colorectal Cancer Database including patients undergoing intended curative elective colonic cancer surgery from January 1, 2010 through December 2013. PATIENTS: A total of 5143 patients (1602 open resections; 3541 laparoscopic resections) with colonic cancer were included. MAIN OUTCOME MEASURES: Risk factors for poor resection quality were identified through uni- and multivariate logistic regression analysis. The surgical approach was assessed by propensity score-matched regression analysis. Poor resection quality was defined as resections in the muscularis plane accompanied by R0 resection, or resections in any resection plane accompanied by R1 resection. RESULTS: Overall, 4415 (85.8%) of the resections were considered good and 728 (14.2%) were considered poor. After multivariate analysis, neoadjuvant oncological treatment, advanced tumor stage (T3-4), advancing N stage (N1-2), open tumor perforation, and open surgery significantly increased the risk of poor resection quality. In a propensity score-matched sample (n = 1508 matched pairs), matched for age, sex, ASA score, BMI, neoadjuvant treatment, tumor stage, and tumor location, open resection was still associated with a higher risk of poor resection quality compared with laparoscopic resection (OR, 1.4; 95% CI, 1.1–1.8; p = 0.002). LIMITATIONS: Retrospective design was a limitation of this study. CONCLUSIONS: In this nationwide propensity score-matched database study, laparoscopic resection was associated with a higher probability of good resection quality compared with open resection for colonic cancer. Risk factors for compromised specimen quality were neoadjuvant oncological treatment, locally advanced tumor stage (T3-4), advanced N stage (N1-2), open tumor perforation, and open surgery. See Video Abstract at http://links.lww.com/DCR/A830.