In stroke and other medical illnesses, secondary depression may be associated with different factors in women than in men. The authors examined 301 consecutive admissions for acute treatment of cerebrovascular accident for gender differences in depression, psychosocial factors, physical impairment, and lesion location. Women were twice as frequently diagnosed with major depression as men. Women with major depression had a greater frequency of left hemisphere lesions than men. In men, major depression was associated with greater impairment in activities of daily living, and greater severity of depression was associated with greater impairment in daily activities and social functioning. In women, greater severity of depression was associated with prior diagnosis of psychiatric disorder and cognitive impairment. These findings suggest a different nature of poststroke depression in men and women and may have implications for its treatment.