The effects of vitamins and beta-carotene on the risk of colorectal adenomas have not been fully investigated. Recent data suggest that smoking could modulate the effect of beta-carotene supplements on adenoma recurrence. We investigated the effect of dietary vitamins and beta-carotene on the risk of adenomas, and a potential interaction with smoking status as part of a case-control study of environmental factors associated with the risk of colorectal adenomas and cancers. We compared nutrient intakes in polyp-free controls (n = 427) and adenoma cases (n = 362) globally and using models stratified by smoking status, adjusted for age, sex, BMI, and energy and alcohol intakes. Folate and vitamins C and B-6 were inversely related to adenoma risk (P for trend = 0.005, 0.03, and 0.02, respectively), whereas vitamin D tended to be inversely associated with risk (P for trend = 0.05). There was a significant interaction between beta-carotene and smoking (P interaction = 0.04). In nonsmokers, beta-carotene was inversely associated with adenoma risk, especially that of colon adenomas [odds ratios (ORs) in low vs. high consumers and 95% CI 0.4 (0.2-0.9)], whereas in past or current smokers, beta-carotene was associated with a nonsignificant (P for trend = 0.19) increase in the risk of colon adenomas [corresponding OR = 1.9 (95% CI = 0.9-4.1)]. Our findings support a protective effect of folate and vitamins C and B-6 irrespective of smoking habits, and a protective effect of beta-carotene in nonsmokers only. They suggest an adverse effect of beta-carotene in smokers, who should be cautious about taking high doses of this micronutrient.