We investigated the associations between dietary intake of folate and vitamin B2, MTHFR C677T genotype, and colorectal adenomas in a Dutch case-control study. Data of cases with at least one histologically confirmed colorectal adenoma (n = 768) and controls with no history of any type of colorectal polyp (n = 709) were included. Dietary intake was assessed using a food-frequency questionnaire. Multivariable models included age and, if appropriate, dietary folate and calcium intake. The adjusted odds ratio (OR) and 95% confidence interval (CI) for the highest compared with the lowest sex-specific tertile of intake were 1.32 (95% CI, 1.01-1.73) for folate and 0.51 (95% CI, 0.36-0.73) for vitamin B2. Folate seemed to be a risk factor, especially when vitamin B2 intake was low; vitamin B2 was inversely associated with adenomas, especially with relatively high folate intake. No association was observed between MTHFR C677T genotype and colorectal adenomas. The inverse association between vitamin B2 intake and colorectal adenoma risk seemed to be more pronounced among those with the MTHFR TT genotype. We conclude that this study does not provide evidence for a decreased colorectal adenoma risk for subjects with high dietary intake of folate. It suggests, however, an inverse association between vitamin B2 and colorectal adenomas, which may be more relevant for those with the MTHFR TT genotype.