Background and aim  Removal of polyps during colonoscopy effectively prevents the development of colorectal cancer. So far, snare resection with high frequency current with or without prior submucosal saline injection is the method of choice. The aim of this study was to evaluate the feasibility, safety, and outcome of cold snare resection during routine endoscopy. Methods  In this prospective study, 522 patients undergoing outpatient colonoscopy were included. Cold snare resection for diminutive (< 6 mm), small (6 – 9 mm), and larger polyps (> 9 – 15 mm) was performed using a dedicated cold snare device (Exacto ® ) without prior submucosal injection. Outcome parameters included bleeding rate, perforation rate, procedure time, histologic evaluation of polyp margins, and success rates. The data were compared to a group of patients undergoing hot snare resection. Results  Overall, 1233 polyps were removed using cold snare resection with an overall success rate of 99.4 %. All failures of cold snare resection occurred in the cecum (8/82, failure rate 9.8 %). In the remaining colon, the success rate was 100 %. Immediate post-polypectomy bleeding occurred in 0.49 % of all patients and was most frequently seen in polyps larger than 9 mm. The procedure time was significantly shorter using cold snare resection compared with hot snare resection (27.6 min vs. 35.7 min, P  < 0.01). Conclusion  Cold snare resection can be performed safely in outpatients for removal of small polyps in screening colonoscopy. It does not require prior saline injection and reduces procedure time without an increased risk of bleeding.