BACKGROUND: A water method developed to attenuate discomfort during colonoscopy enhanced cecal intubation in unsedated patients. Serendipitously a numerically increased adenoma detection rate (ADR) was noted. OBJECTIVE: To explore databases of sedated patients examined by the air and water methods to identify hypothesis-generating findings. DESIGN: Retrospective analysis. SETTING: VA endoscopy center. PATIENTS: creening colonoscopy. INTERVENTIONS: From 1/2000-6/2006 the air method was used - judicious air insufflation to permit visualization of the lumen to aid colonoscope insertion and water spray for washing mucosal surfaces. From 6/2006-11/2009 the water method was adopted - warm water infusion in lieu of air insufflation and suction removal of residual air to aid colonoscope insertion. During colonoscope withdrawal adequate air was insufflated to distend the colonic lumen for inspection, biopsy and polypectomy in a similar fashion in both periods. Main outcome measurements: ADR. RESULTS: The air (n=683) vs. water (n=495) method comparisons revealed significant differences in overall ADR 26.8% (183 of 683) vs. 34.9% (173 of 495) and ADR of adenomas >9 mm, 7.2% vs. 13.7%, respectively (both P<0.05, Fisher's exact test). LIMITATIONS: Non-randomized data susceptible to bias by unmeasured parameters unrelated to the methods. CONCLUSION: Confirmation of the serendipitous observation of an impact of the water method on ADR provides impetus to call for randomized controlled trials to test hypotheses related to the water method as an approach to improving adenoma detection. Because of recent concerns over missed lesions during colonoscopy, the provocative hypothesis-generating observations warrant presentation.