BACKGROUND Young adults aged from 18 to 44 years comprise a large portion of the population suffering from depression. Yet few studies have compared the likelihood of dying of natural causes or by suicide among depressed patients. This study uses a case-control approach to compare the likelihood of dying of natural causes and by suicide for depressed and non-depressed patients based on a representative national sample in Taiwan. METHODS A retrospective case-control study design was used to analyze two nationwide population-based datasets: the National Health Insurance Research Database (NHIRD) and the official Cause of Death data file in Taiwan. The study cohort consisted of 827 patients from 18 to 44 years old who were hospitalized with a primary diagnosis of depressive disorder from 1998-2003. A comparison cohort of patients hospitalized for appendectomies was matched with the study sample in terms of age and gender (N=2481). RESULTS After adjusting for the age and comorbid medical disorders, the hazard of dying during the five-year follow-up period was 1.72 times greater for depressed patients than for appendectomy patients. Depressed patients were more likely to die by suicide during the follow-up period, as no significant difference in odds of dying from natural causes was observed between these two cohorts. CONCLUSIONS Further studies should be initiated to identify specific risk factors for suicide among younger adults, while prevention strategies might focus on stresses associated with particular life stages, taking age and gender patterns into account.