Background An observational study in veterans showed that a novel water method (water infusion in lieu of air insufflation) enhanced cecal intubation and willingness to undergo a repeat scheduled unsedated colonoscopy. Objective To confirm these beneficial effects and significant attenuation of discomfort in a randomized, controlled trial (RCT). Design Prospective RCT, intent-to-treat analysis. Setting Veterans Affairs ambulatory care facility. Patients Veterans undergoing scheduled unsedated colonoscopy. Interventions During insertion, the water and traditional air methods were compared. Main Outcome Measurements Discomfort and procedure-related outcomes. Results Eighty-two veterans were randomized to the air (n = 40) or water (n = 42) method. Cecal intubation (78% vs 98%) and willingness to repeat (78% vs 93%) were significantly better with the water method ( P < .05; Fisher exact test). The mean (standard deviation) of maximum discomfort (0 = none, 10 = most severe) during colonoscopy was 5.5 (3.0) versus 3.6 (2.1) P = .002 (Student t test), and the median overall discomfort after colonoscopy was 3 versus 2, P = .052 (Mann-Whitney U test), respectively. The method, but not patient characteristics, was a predictor of discomfort ( t = −1.998, P = .049, R2 = 0.074). The odds ratio for failed cecal intubation was 2.09 (95% CI, 1.49-2.93) for the air group. Fair/poor previous experience increased the risk of failed cecal intubation in the air group only. The water method numerically increased adenoma yield. Limitations Single site, small number of elderly men, unblinded examiner, possibility of unblinded subjects, restricted generalizability. Conclusions The RCT data confirmed that the water method significantly enhanced cecal intubation and willingness to undergo a repeat colonoscopy. The decrease in maximum discomfort was significant; the decrease in overall discomfort approached significance. The method, but not patient characteristics, was a predictor of discomfort. (Clinical trial registration number NCT00747084 ).