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Colorectal cancer is the third most common form of cancer and the fourth most frequent cause of cancer deaths worldwide. The association between cigarette smoking and colorectal cancer has been inconsistent among studies.To clarify the association of cigarette smoking and colorectal cancer, we performed a comprehensive literature search and a meta-analysis of observational studies considering both incidence and mortality.We performed a literature search using PubMed, ISI Web of Science (Science Citation Index Expanded), and EMBASE to May 2008, with no restrictions. We also reviewed references from all retrieved articles.All articles that were independent and contained the minimum information necessary to estimate the colorectal cancer risk associated with cigarette smoking and a corresponding measure of uncertainty.Articles were reviewed and data were extracted and cross-checked independently by 3 investigators, and any disagreement was resolved by consensus among all 3.One hundred six observational studies were included in the analysis of incidence. Twenty-six studies provided adjusted risk estimates for ever smokers vs never smokers, leading to a pooled relative risk of 1.18 (95% confidence interval [CI], 1.11–1.25). Smoking was associated with an absolute risk increase of 10.8 cases per 100 000 person-years (95% CI, 7.9–13.6). We found a statistically significant dose-relationship with an increasing number of pack-years and cigarettes per day. However, the association was statistically significant only after 30 years of smoking. Seventeen cohort studies were included in the analysis of mortality. The pooled risk estimate for ever vs never smokers was 1.25 (95% CI, 1.14–1.37). Smoking was associated with an absolute risk increase of 6.0 deaths per 100 000 person-years (95% CI, 4.2–7.6). For both incidence and mortality, the association was stronger for cancer of the rectum than of the colon.Cigarette smoking is significantly associated with colorectal cancer incidence and mortality.