Except for gallstones, the risk factors for cancers of the biliary tract (CBTs) are poorly understood. Recent case-control studies have suggested cigarette smoking as a potential risk factor. In a cohort study of nearly 250,000 US veterans whose mortality was followed for up to 26 years, we evaluated the risk of CBT associated with tobacco use. Relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated. A total of 303 CBT deaths were observed during the follow-up period. Compared with those who had never used any tobacco, current cigarette smokers at entry to the cohort had a 50% excess risk of CBT (RR = 1.5, CI = 1.1-2.0). A nearly 2-fold risk was observed among those who smoked more than 20 cigarettes per day and among those who started smoking under age 20. Non-significant increases in risk occurred among smokers of other forms of tobacco. This cohort study is consistent with reports that smoking is a risk factor for CBT, but further studies are needed to clarify whether the effect is specific for certain subsites and whether it reflects an association with pre-existent gallstones.