Prior studies have shown an increased risk of colorectal cancer following cholecystectomy, but few studies have explored the association between cholecystectomy and the risk of colorectal adenomas. We used data from three large randomized adenoma chemoprevention trials to explore the association between cholecystectomy and the occurrence of adenomas. After adjusting for confounding factors, we found no increased risk for adenomas among individuals who had undergone cholecystectomy [risk ratio (RR), 1.02; 95% confidence interval (95% CI), 0.88-1.18]. There was a slight increase in the risk of advanced recurrent adenomas (RR, 1.28; 95% CI, 0.94-1.76) and multiple advanced recurrent adenomas (RR, 1.34; 95% CI, 0.97-1.85) but the 95% CIs included the null in both cases. We conclude that the increased risk for colorectal cancer following cholecystectomy seems to be due to a biological process occurring after the adenoma has developed.