The novel antidepressant trazodone is hypothesized to be less cardiotoxic than the tri-tetracyclic antidepressants. Recently, however, 2 patients with preexisting ventricular irritability showed an increased number of ventricular premature beats and of repetitive forms after starting on trazodone. Data are presented here from four studies on the cardiovascular safety of trazodone. Conclusions are: (1) Trazodone has little effect on cardiac conduction. (2) Trazodone does not worsen supraventricular arrhythmias. (3) Trazodone produces less postural hypotension than most other antidepressants and it tends to lower heart rate. (4) Lower doses of trazodone (100-300 mg) are better tolerated and more effective in major depressives simultaneously debilitated by significant cardiovascular disease. (5) It is possible that the so-called ‘trazodone aggravation’ of ventricular irritability is a statistical artifact - although further research is needed to verify this conclusion, and in the meantime the drug should be used with caution in such patients.