The authors evaluated alcohol drinking and cigarette smoking in relation to risk of colorectal polyps in a Nashville, Tennessee, colonoscopy-based case-control study. In 2003-2005, cases with adenomatous polyps only (n = 639), hyperplastic polyps only (n = 294), and both types of polyps (n = 235) were compared with 1,773 polyp-free controls. Unordered polytomous logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals. Consumption of at least five alcoholic drinks per week was not strongly associated with development of polyps. Odds ratios for all polyp types were increased for dose, duration, and pack-years of cigarette smoking and were stronger for hyperplastic polyps than for adenoma. Compared with never smoking, dose-response relations were particularly strong for current smoking and duration; for > or =35 years of smoking, odds ratios were 1.9 (95% confidence interval (CI): 1.4, 2.5) for adenomatous polyps only, 5.0 (95% CI: 3.3, 7.3) for hyperplastic polyps only, and 6.9 (95% CI: 4.4, 11.1) for both types of polyps. Compared with current smoking, time since cessation was associated with substantially reduced odds; for > or =20 years since quitting, odds ratios were 0.4 (95% CI: 0.3, 0.6) for adenoma only, 0.2 (95% CI: 0.1, 0.3) for hyperplastic polyps only, and 0.2 (95% CI: 0.2, 0.4) for both polyp types. These findings support the adverse role of cigarette smoking in colorectal tumorigenesis and suggest that quitting smoking may substantially reduce the risk of colorectal polyps.