AbstractIntroduction The primary aim of this study was to explore the incidence rate of erectile dysfunction (ED) among major depressive disorder (MDD) patients in an Asian country. The second aim was to compare the risk of ED in MDD patients that were treated using antidepressants with a high risk-ED, antidepressants with a low risk-ED, or without treatment. Methods We identified 4339 male patients with newly diagnosed MDD using the National Health Database. Four matched controls per case were selected for the study. Results The mean age of the participants was 42.3±16.9. A higher crude HR of 3.6 (95% CI: 2.8–4.6) was seen in the male patients with MDD. After adjusting for obesity, monthly income, urbanization level, and comorbidity, the MDD patients had a 3.2-fold higher HR for an ED diagnosis than the controls. Patients with untreated depression had the highest risk of ED, compared to the control group (HR=3.9). Patients treated with IHiRA had a medium risk of developing ED (HR=3.6), and patients treated with ILoRA had the lowest risk of ED (HR: 2.5). Conclusion This prospective cohort study found an association between ED and prior MDD. Patients with untreated depression may have the highest risk of developing ED.