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To determine the number of pack-years exposure associated with a 2-fold increase risk for significant colorectal neoplasia and to examine the risk of smoking in younger patients.Cigarette smoking has been shown to be a significant risk factor for colorectal neoplasia and may be used to stratify patients for screening or triaging of screening resources. However, more information is needed regarding the amount of exposure required to significantly increase by 2-fold an individual's risk for colorectal neoplasia.Data collected for 2707 patients presenting for screening colonoscopy included tobacco use measured in pack-years and known risk factors for colorectal neoplasia. Our outcome was endoscopically detected significant colorectal neoplasia that included large (>1 cm) tubular adenomas, villous adenomas, multiple (3 or more) adenomas, high-grade dysplasia, and adenocarcinoma.Patients who smoked more than 30 pack-years were more than 2 times more likely to have significant colorectal neoplasia than patients who never smoked (odds ratio: 2.40; 95% confidence interval: 1.65-3.50). For patients aged 40 to 49 years, smokers were more likely than nonsmokers to have significant colorectal neoplasia (odds ratio: 2.71; 95% confidence interval: 1.05-6.97).Patients who have smoked more than 30 pack-years had a more than 2-fold increase for significant colorectal neoplasia as compared with nonsmokers. The increased risk was also observed in younger patients. Our data have implications for screening guidelines.