We conducted a systematic review of studies addressing the relation between cigarette smoking and gastric cancer to estimate the magnitude of the association for different levels of exposure and cancer locations. Published cohort, case-cohort, and nested case-control studies were identified through PubMed, Scopus, and Web of Science searches, from inception to July 2007. Relative risk (RR) estimates referring to the comparison of two categories of exposure (e.g., current smokers vs. never smokers) were combined using a random effects model. Generalized least squares regression was used for trend estimation. Heterogeneity was quantified using the I (2) statistic. Forty-two articles were considered for the systematic review. Comparing current smokers with never smokers: the summary RR estimates were 1.62 in males (95% CI: 1.50-1.75; I (2) = 46.0%; 18 studies) and 1.20 in females (95% CI: 1.01-1.43; I (2) = 49.8%; nine studies); the RR increased from 1.3 for the lowest consumptions to 1.7 for the smoking of approximately 30 cigarettes per day in the trend estimation analysis; smoking was significantly associated with both cardia (RR = 1.87; 95% CI: 1.31-2.67; I (2) = 73.2%; nine studies) and non-cardia (RR = 1.60; 95% CI: 1.41-1.80; I (2) = 18.9%; nine studies) cancers. Our study provides solid evidence to classify smoking as the most important behavioral risk factor for gastric cancer.