OBJECTIVE — To assess the association between antidepressant medicine use and risk of developing diabetes during the Diabetes Prevention Program (DPP) and Diabetes Prevention Program Outcomes Study (DPPOS). RESEARCH DESIGN AND METHODS — DPP/DPPOS participants were assessed for diabetes every 6 months and for antidepressant use every 3 months in DPP and every 6 months in DPPOS for a median 10.0-year follow-up. RESULTS — Controlled for factors associated with diabetes risk, continuous antidepressant use compared with no use was associated with diabetes risk in the placebo (adjusted hazard ratio 2.34 [95 % CI 1.32–4.15]) and lifestyle (2.48 [1.45–4.22]) arms, but not in the metformin arm (0.55 [0.25–1.19]). CONCLUSIONS — Continuous antidepressant use was significantly associated with diabe-tes risk in the placebo and lifestyle arms. Measured confounders and mediators did not account for this association, which could represent a drug effect or reflect differences not assessed in this study between antidepressant users and nonusers. Diabetes Care 33:2549–2551, 2010 Our earlier report from the DiabetesPrevention Program (DPP) (1) wasthe first to examine antidepressant medicine (ADM)-related diabetes risk in an overweight population with elevated fasting glucose and impaired glucose tol-erance. We found in the placebo and life-style arms that when other factors associated with diabetes risk (age, sex, ed-ucation, fasting plasma glucose at base-line, weight at baseline, weight change during the study, and depression symp-toms at baseline and during the study) were controlled, baseline ADM use and continuous ADM use during the study (compared with no use) were associated with significantly increased diabetes risk; in the lifestyle arm, intermittent ADM use during the study was also associated with increased diabetes risk. Among met-formin arm participants, ADM use was not associated with developing diabetes. The present study extends the dura-tion of follow-up in our previous report by including 7 years of the Diabete