BACKGROUND: The relationship between the use of anti-hypertensive drugs and cancer risk remains controversial. The main objective of this study was to assess the potential effect of beta-blocker use on cancer risk. METHODS: In a cohort of 839 patients with cardiovascular disease, followed up prospectively for an average period of 10 years, cancer occurrence was recorded according to the exposure to beta-blockers. The relative risk of cancer associated with beta-blocker use was estimated using a Cox model adjusted on gender and age. Ever- vs never-use of beta-blockers and duration of exposure to the drug were analyzed as time-dependent variables. In addition, the standardized incidence ratios (SIR) were calculated using the corresponding age- and gender-adjusted cancer incidences in the French general population. RESULTS: A total of 326 beta-blocker users and 513 users of other treatments were included in the cohort. During the follow-up period, representing 8,466 person-years, incident cancer cases were 15 and 59 in beta-blocker ever-users versus never-users, respectively. Using the Cox model, the overall relative risk of cancer was 0.51 (95% confidence interval [95% CI]: 0.29-0.90) in the beta-blocker ever-users versus never-users (p=0.02), with a 6% decrease per year of use (95% CI: 1%-12%; p=0.03). The corresponding SIR ratio between these two groups was 0.44 (95% CI: 0.24-0.76). CONCLUSION: In this cohort, the beta-blocker treatments appeared to decrease the cancer risk significantly. However, this result should be considered with caution; further work is needed, as some sources of bias associated with this type of epidemiological study cannot be totally excluded.