BACKGROUND: Non-institutionalised patients treated with antidepressants have been shown to have indicators of a generalised vulnerability, such as high rates of health service use and excessive prescription drug use. Therefore, mortality in this patient group is of interest. METHOD: All first-incidence antidepressant users in a defined population during a five-year period were identified. Their total mortality during a nine-year follow-up was analysed. Cox proportional hazards regression was used to analyse total mortality, and mortality in cardiovascular disease, controlling for baseline chronic medical disease. RESULTS: Antidepressant treatment at the index date was a statistically significant predictor for increased long-term mortality in the over-65s, even when controlling for pre-existing chronic medical disease. Baseline ischaemic heart disease and concurrent antidepressant treatment significantly predicted mortality from cardiovascular causes. CONCLUSION: Prescribed antidepressant treatment identifies patients who are at risk of increased mortality. For the physician in ambulatory care, knowledge of a patient's antidepressant treatment history may be a valuable tool in managing patient care.