OBJECTIVE: Although evidence exists linking smoking to precancerous colorectal adenomatous polyps, few studies have examined the association between cigarette smoking and recurrence of colorectal polyps. This association was investigated prospectively with data from the Polyp Prevention Trial. METHODS: Cigarette smoking data were collected through baseline interviews. The study was completed by 1872 men and women with presence of adenomas at baseline colonoscopy. Multiple logistic regression analysis was used to examine the association between cigarette smoking and polyp recurrence (adenomatous and hyperplastic) up to four years from baseline. RESULTS: Adenoma recurrence was not related to cigarette smoking. Current smokers had increased odds of hyperplastic polyps at follow-up compared to never smokers (OR 2.88, 95% CI 2.06-4.01). Current smoking was associated with subsequent distal (OR 3.44, 95% CI 2.38-4.95) and rectal (OR 3.53, 95% CI 2.15-5.78) hyperplastic polyps, but not subsequent proximal hyperplastic polyps. Cigarette smoking was associated with subsequent multiple and small size (4 mm) hyperplastic polyps. Significant linear trends were observed between development of subsequent hyperplastic polyps and all smoking variables. CONCLUSIONS: Although no association with recurrent adenomas was observed, cigarette smoking was significantly associated with hyperplastic polyp development, except for those in the proximal colon. This prospective study confirms that cigarette smoking has a significant effect on the development of hyperplastic colorectal polyps.