OBJECTIVES: To determine whether: 1) use of antidepressants, compared to benzodiazepines,  increases the risk of type 2 diabetes mellitus; 2) individual antidepressant classes, compared to benzodiazepines, increases the risk of type 2 diabetes; and 3) there are differences in the risk of type 2 diabetes among antidepressant classes.  METHODS: A retrospective cohort study using the Texas Medicaid prescription claims database was conducted from January 1, 2002 to December 31, 2009. Patients aged 18-64 years with new prescriptions for antidepressant agents (exposed) and benzodiazepines (unexposed) and without diabetes at cohort entry constituted the base study population.  Logistic regression analyses were used to address the study objectives. RESULTS: A total of 44,715 patients formed the study sample. Of these, 35,552 were exposed and 9,163 were unexposed. The average age was 38.6 (SD=14.2) and the majority (69.3%) were female. Use of antidepressants was associated with an increased risk of diabetes (Relative Risk [RR] = 1.396; 95% Confidence Interval [CI]: 1.126 – 1.729) compared to benzodiazepine use, after controlling for age, gender, medication adherence, persistence, number of diabetogenic medications, Chronic Disease Score, treatment duration, and year of cohort entry. Compared to benzodiazepines, tricyclic antidepressants (TCAs; RR=1.445; 95% CI: 1.057 – 1.977), serotonin-norepinephrine reuptake inhibitors (SNRIs; RR=1.593; 95% CI: 1.160 – 2.186), and selective serotonin reuptake inhibitors (SSRIs; RR=1.317; 95% CI: 1.037 – 1.673), were associated with an increased risk for diabetes. Compared to TCAs, there were no significant differences in the risk of diabetes for SSRIs (RR=0.876; 95% CI: 0.678 – 1.132), SNRIs (RR=1.003; 95% CI: 0.734 – 1.371) and Other antidepressants (RR=0.785; 95% CI: 0.582 – 1.058). CONCLUSIONS: Overall, use of antidepressants was associated with an increased risk of diabetes mellitus compared to benzodiazepine use. This association was also observed when tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors were compared to benzodiazepines.