Background and Aims The prevalence of advanced histology in flat adenomas is uncertain. There are limited data on the prevalence of synchronous adenomas in patients with flat adenomas. The aims of this study were to determine whether the flat adenomas harbor advanced histology more than the polypoid adenomas and whether the presence of flat adenomas is an independent predictor of synchronous adenomas. Methods A retrospective analysis of data from 3 prospective clinical trials conducted at 2 tertiary care referral centers that included patients undergoing screening or surveillance colonoscopy was performed. The location, size, and morphology of each polyp resected was documented and sent for histopathological examination in a unique specimen jar. Results A total of 2931 polyps were removed in 1340 patients. Of the 1911 adenomas (65.2%), 293 (15.3%) were flat and 1618 (84.7%) were polypoid. The prevalence of advanced histology did not differ between flat and polypoid adenomas (1.4% vs 3.1%; P =.13). Multivariate analysis confirmed that the presence of at least 1 flat adenoma was a predictor of the presence of a large adenoma (P <.01; odds ratio [OR], 2.80; 95% CI, 1.86-4.22), advanced adenoma (P <.01; OR, 2.70; 95% CI, 1.80-4.06), and 3 or more adenomas (P <.01; OR, 2.44; 95% CI, 1.66-3.59). Conclusion Although the prevalence of advanced histology in flat adenomas is similar to that of polypoid adenomas, flat adenomas are associated with increased prevalence of synchronous large and advanced adenomas. Whether these results imply shorter surveillance intervals in patients with flat adenomas needs to be explored in future studies.