Background: Professional truck drivers are at high risk of chronic diseases. Further examination of tobacco use and its impact on oral health is warranted – both in terms of the direct association between tobacco use and poor oral health, and in terms of tobacco use being an indicator of poor health behaviors. Objective: To estimate the possible association between smoking and dental caries experience in a population with high tobacco use. Methods: Drivers’ licenses are periodically re-issued by the Mexican government and as part of the licensing process a physical exam takes place. We administered a free, standardized questionnaire together with an oral examination (WHO criteria) included in the physical exam, targeting a random sample of applicants in Mexico City. Results: A total of 824 dentate males (mean age 35.5 ± 10 years) took part in the study, of whom 49.2% were current smokers and 23.2% were former smokers. Caries experience was mean DMFT 8.95 (± 6.05). Only 18.0% of participants had ‘excellent’ or ‘good’ oral hygiene. The prevalence of ‘large’ cavities increased as the number of cigarettes/day increased from 14.6% (1–3 cigarettes/day) to 33.3% (≧10 cigarettes/day). Using multiple linear regressions, we found that older age, poorer oral hygiene, higher education, and greater tobacco exposure were significantly associated with higher caries experience (DMFT). An interaction was observed with oral hygiene and tobacco: drivers that smoked and had ‘poor’ oral hygiene showed the highest number of large cavities and missing teeth. Health promotion interventions are needed in this at-risk population group.