The objective of this study was to evaluate the impact of a comprehensive anti-smoking health program conducted over twelve years at a regional university hospital in southern Spain. Prevalence of tobacco was compared retrospectively using data collected during occupational health assessments (n = 4291). Bivariate and logistic regression analyses were carried out to evaluate tobacco consumption differences according to age, sex, professional category, and workplace building. The results show a reduction in the active smoking rate among hospital staff evaluated (from 22.8% to 19.8%) with significant differences between non-health and health workers. Accumulated smoking consumption fell to 13.45 ± 14.60 packs/year with men presenting a higher consumption (p < 0.001). The predictive variables of tobacco use were sex (greater consumption among men, p = 0.021), number of cigarettes (greater consumption among professionals who smoked less than 1 pack/day, p < 0.001), and time smoking (greater use among professionals with more than 10 years smoking, p < 0.001). There was a higher rate of staff smokers at the hospital building with a majority of mental health inpatients. This study provides a practical example of making the optimum use of digital medical records in the evaluation of a comprehensive anti-smoking health program.