Background: Abdominal pain after colonoscopy is a common, distressing symptom resulting from bowel distension by insufflated gas. CO₂, unlike air, is rapidly cleared from the colon by passive absorption. A commercially available CO₂ delivery system has only recently become available. The effects of CO₂ and air insufflation on residual bowel gas and postprocedure pain were compared. Methods: One hundred patients were randomized to undergo colonoscopy with insufflation of air (n = 51) or CO₂ (n = 49) by means of a regulator; 97 patients completed the study. Patients with active GI bleeding, inflammatory bowel disease, or previous colectomy were excluded. Pain scores (ordinal scale: 0 = none, to 5 = extreme) were recorded immediately after colonoscopy and at 1, 6, and 24 hours. Residual colonic gas was evaluated on abdominal radiographs at 1 hour. Results: Residual colonic gas and postprocedural pain at 1 and 6 hours were significantly less in the CO₂ group. 71% of patients insufflated with room air had colonic distension in excess of 6 cm versus 4% for those in the CO₂ group. 94% of patients insufflated with CO₂ had minimal colonic gas versus 2% in whom air was used (p < 0.0001). Of patients insufflated with air, 45% and 31% had pain at, respectively, 1 hour and 6 hours, versus 7% and 9%, respectively, for those insufflated with CO₂ (respectively, p < 0.0001 and p < O.02). No complications resulted from use of the CO₂ delivery system. Conclusions: Insufflation of CO₂ rather than air significantly reduces abdominal pain and bowel distension after colonoscopy. CO₂ may be insufflated safely and effectively with the new CO₂ delivery system. (Gastrointest Endosc 2002;56:190-4.)