The antidepressant efficacy and cardiac safety of trimipramine were evaluated in 22 depressed patients with mild heart disease (New York Heart Association class I, II, or III) who received doses of 50 to 200 mg/day for 28 days. Efficacy was evidenced by a significant decrease from baseline in Hamilton Rating Scale for Depression scores. The only significant change from baseline in electrocardiographic, Holter monitor, myocardial function, or vital sign evaluations was a transient prolongation of the mean QRS interval. None of the adverse reactions involved the cardiovascular system. The results demonstrate that trimipramine is effective in the treatment of depression and is not likely to produce serious or harmful cardiovascular side effects in patients with mild heart disease.