OBJECTIVE : This study aims to investigate the risk of hyperglycemic crisis episode (HCE) in diabetic patients with depression and to examine the relationship between the duration of antidepressants use and the risk of HCE. METHODS : In all, 26,746 diabetic patients with depression and 106,853 controls (without depression) matched by gender, age, index year, and Charlson Comorbidity Index (CCI) score were included between 1999 and 2010, then followed until the end of 2013. During the follow-up period, participants who developed HCE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the HCE incidence rate between the two groups studied. RESULTS : Diabetic patients with depression had a significantly increased risk of HCE compared to unaffected controls after adjusted for gender, age, CCI score, and duration of antidepressants use (2.87 versus 2.50 per 1000 person-years, HR: 1.78, 95% CI: 1.56-2.03). Also, long-term use of antidepressants in diabetic patients with depression showed a significantly reduced risk of HCE compared to non-users after adjusting for the above-mentioned variables (HR: 0.44, 95% CI: 0.35-0.55). CONCLUSIONS : This study shows diabetic patients with depression have an increased risk of HCE, and the use of antidepressants may reduce its risk.