The authors sought to determine the relative efficacy and tolerability of duloxetine versus citalopram and sertraline in the treatment of poststroke depression (PSD), anxiety, and fatigue. A group of 60 patients with PSD were assigned to receive duloxetine, citalopram, or sertraline and were assessed over a 3-month period for depression, anxiety, and fatigue. Improvement of depression and anxiety, but not fatigue, was observed in all study groups. Duloxetine was well tolerated and significantly more effective than citalopram and sertraline for the treatment of anxiety symptoms in PSD patients. None of the antidepressants used was effective for reducing symptoms of fatigue.