Our aim was to investigate the association of calcium channel blocker (CCB), beta-blocker, and ACE inhibitor medications with the risk of depression in diabetic patients. A case-control study was performed using an automated database (MediPlus, IMS) of 400 primary care practices in Germany including 972 diabetic cases with newly diagnosed depression in 1996 (index date) and 972 diabetic controls, matched for age, sex, and index date. The odds ratios (95%-confidence intervals) for depression, adjusted for type of practice, number of visits and prescriptions, hospitalization, cardiovascular diagnoses, and renal failure, were 2.2 (95% CI: 1.2-4.2) for exposure to CCB 6 months prior to index date, 2.6 (95% CI: 1.1-7.0) for beta-blockers, and 1.3 (95% CI: 0.8-2.2) for ACE inhibitors, respectively. Adjusted odds ratio for CCB (4.3; 95% CI: 1.7-13.5) and beta-blockers (4.5; 95% CI: 1.2-29.5) were higher with daily dosages above the median. Prescriptions of CCB and beta-blockers among diabetic patients may increase the risk of depression. Because this association may alternatively be explained by cardiovascular comorbidity, further studies will be necessary to investigate the link between these cardiovascular medications and depression.