INTRODUCTION: Data supporting endoscopic resection (ER) over surgical resection (SR) for large and complex polyps come from high-volume centers. The aim of this study was to determine whether these favorable outcomes can be replicated among endoscopists at tertiary Veterans Affairs Medical Centers (VAMCs) who perform 25 to 30 ER cases a year. METHODS: Patients with adenomatous polyps or intra-mucosal cancers ≥ 2 cm in size who underwent ER or SR were identified from prospectively maintained databases at the 2 tertiary VAMCs in Veterans Integrated Service Network 6 (VISN6). The primary outcome was the rate of serious complications in the ER and SR groups. RESULTS: 310 ER and 81 SR patients met the inclusion criteria. ER was successful in 97% of all polyps, and 93% of polyps ≥ 4 cm. The rate of serious complications was significantly lower with ER compared to SR (0.6% vs. 22%, p = 0.00001). These findings persisted even after limiting the analysis to polyps ≥ 4 cm and after propensity score matching. If all ER patients had instead undergone laparoscopic surgery, the estimated risk of a serious complication was still higher than ER for all patients (8% vs. 0.6%, p < 0.0001) but not significantly higher for polyps ≥ 4 cm (8% vs 2%, p = 0.17). CONCLUSIONS: This study documents high success rates for ER in veterans with colorectal polyps ≥ 2 cm and ≥ 4 cm. When compared to a historical cohort of surgical patients, a strategy of attempting ER first reduced morbidity. A randomized trial is warranted to compare ER to laparoscopic surgery for polyps ≥ 4 cm.