OBJECTIVE This study compared the long-term efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) with sertraline in patients with diabetes and depression who initially responded to short-term depression treatment. RESEARCH DESIGN AND METHODS A randomized controlled single-blind trial was conducted in 70 secondary care centers across Germany comparing 12 weeks of CBT with sertraline in 251 patients with type 1 or 2 diabetes (mean HbA1c 9.3%, 78 mmol/mol) and major depression (Structured Clinical Interview for DSM-IV [SCID]). After 12 weeks, treatment responders (≥50% reduction Hamilton Depression Rating Scale [HAMD-17]) were included in the 1-year study phase where CBT patients were encouraged to use bibliotherapy and sertraline patients received continuous treatment. We analyzed differences for HbA1c (primary outcome) and reduction (HAMD-17) or remission (SCID) of depression from baseline to the 1-year follow-up using ANCOVA or logistic regression analysis. RESULTS After 12 weeks, 45.8% of patients responded to antidepressant treatment and were included in the 1-year study phase. Adjusted HbA1c mean score changes from baseline to the end of the long-term phase (−0.27, 95% CI −0.62 to 0.08) revealed no significant difference between interventions. Depression improved in both groups, with a significant advantage for sertraline (HAMD-17 change: −2.59, 95% CI 1.15–4.04, P < 0.05). CONCLUSIONS Depression improved under CBT and sertraline in patients with diabetes and depression, with a significant advantage for sertraline, but glycemic control remained unchanged. CBT and sertraline as single treatment are insufficient to treat secondary care diabetes patients with depression and poor glycemic control.