OBJECTIVE To evaluate the possible association between benzodiazepine use and subsequent cancer risk in Taiwan. METHOD In this population-based retrospective cohort study, we used data from 1996 to 2000 from the Taiwanese National Health Insurance system to investigate the possible association between benzodiazepine use and cancer risk. The exposure cohort (mean age = 47.9 years, standard deviation [SD] = 17.3 years) consisted of 59,647 patients with benzodiazepine use. Each patient from the exposure cohort was randomly frequency-matched by age and sex to a person from the cohort with no benzodiazepine exposure (the comparison group; mean age = 46.4 years, SD = 17.8 years). Each study subject was followed until a diagnosis of cancer was made (according to ICD-9-CM) or until the time the subject was censored for loss to follow-up, death, or termination of insurance-or to the end of 2009. A Cox proportional hazard regression analysis was conducted to estimate the effects of benzodiazepine use on cancer risk. RESULTS In the group with benzodiazepine use, the overall risk of developing cancer was 19% higher than in the group without benzodiazepine exposure, and the difference between the groups was statistically significant (hazard ratio [HR] = 1.19; 99.6% CI, 1.08-1.32). With regard to individual types of cancer, the risk of developing liver cancer (HR = 1.45; 99.6% CI, 1.10-1.90), prostate cancer (HR = 1.72; 99.6% CI, 1.10-2.70), and bladder and kidney cancer (HR = 1.76; 99.6% CI, 1.16-2.67) was significantly higher for the benzodiazepine cohort. CONCLUSIONS This population-based study has shed light on a possible relationship between benzodiazepine use and increased cancer risk. Further large, thorough investigations are needed to confirm these findings.