BACKGROUND: Smoking and alcohol are major causal factors for upper aerodigestive tract cancer, but reliable quantification of the combined impact of smoking and alcohol on this cancer and its major subtypes has not been performed. METHODS: A meta-analysis of studies that had published quantitative estimates of smoking and upper aerodigestive tract cancer by January 2007 was performed. Pooled estimates of relative risks were obtained. Publication bias was investigated through funnel plots and corrected if found to be present. RESULTS: Overall, 85 studies with information on 53,940 individuals with upper aerodigestive tract cancer were included. The pooled estimate for the association between smoking and the risk of this cancer was 3.47 (95% confidence interval, 3.06-3.92). The risk remained elevated for a decade after smoking cessation but declined thereafter. Individuals who both smoked and consumed alcohol had double the risk of upper aerodigestive tract cancer in comparison with those who only smoked: the relative risk was 6.93 (95% confidence interval, 4.99-9.62) for the former and 2.56 (95% confidence interval, 2.20-2.97) for the latter (P < 0.001). CONCLUSIONS: Public health interventions that simultaneously discourage smoking and heavy drinking would have greater benefits than would be expected from those that target only one of these risk factors.