Abstract Background Spain has passed two smoke-free laws in the last years. In 2005, the law banned smoking in indoor places, and in 2010 the ban was extended to outdoor areas of certain premises such as hospitals. This study assesses the impact of smoking consumption among hospital workers at a comprehensive cancer center after the passage of two national smoke-free laws. Methods Six cross-sectional surveys were conducted among a representative sample of hospital workers at a comprehensive cancer center in Barcelona (2001–2012) using a standardized questionnaire. Logistic regression was used to compare differences in the odds of smoking after the laws took effect (baseline vs. 1 st law; 2 nd law vs. 1 st law). Results Baseline smoking prevalence was 33.1%. After passage of the 1 st and 2 nd laws, prevalence decreased, respectively, to 30.5% and 22.2% (p for trend =0.005). Prevalence ratios (PR) indicated a significant decrease in overall smoking after the 2 nd law (PR = 0.65, 95% CI = 0.47-0-89). Smoking dropped in all professional groups, more prominently among those ≥35 years old, doctors, and women. Observed trends over the time included an increase in occasional smokers, a rise in abstinence during working hours but an increase in smoking dependence, and an increase in the employees’ overall support for the smoke-free hospital project. Conclusions A long-term tobacco control project combined with two smoke-free national laws reduced smoking rates among health workers and increased their support for tobacco control policies. The decrease was more significant after the passage of the outdoor smoke-free ban.