Studies have shown fairly consistent positive relationships between smoking and risk of colorectal adenomas, but have yielded inconsistent results for colorectal cancer. Issues relating to the duration, cumulative dose of smoking and the effect of smoking cessation on colorectal cancer risk still need clarification. In a population-based case–control study in Germany, we recruited 540 incident cases of colorectal cancer and 614 controls matched to cases by sex, 5-year age groups and county of residence from January 2003 to June 2004. Subjects were aged ≥30 years, and provided information on risk factors of colorectal cancer, including lifetime cigarette smoking habits, in personal interviews. Odds ratios (OR) and 95% confidence intervals (CI) were computed using conditional logistic regression models, adjusting for potential confounders. Compared with nonsmokers, there was an increased risk for smoking for ≥30 years (OR: 1.25, 95% CI: 0.90–1.75) and a significant risk increase for ≥40 pack-years of smoking (OR: 1.92, 95% CI: 1.13–3.28). Stratification by sex yielded higher risk estimates among females than that among males, with adjusted ORs of 3.5 (95% CI: 1.29–9.52) and 1.15 (0.69–1.91) for women and men, respectively, following ≥30 pack-years of smoking (pinteraction = 0.18). Among smokers, risk reduction was observed after ≥20 years of quitting smoking and was significant for ≥40 years (OR: 0.46; 95% CI: 0.21–0.98), when compared to current smokers (pfor linear trend = 0.05). This study supports the hypothesis that smoking for a long duration at a high cumulative dose increases the risk for colorectal cancer, particularly among women, and suggests that there is risk reduction after longterm smoking cessation.