OBJECTIVE Although psychological stress and smoking have been proposed as factors contributing to Graves' disease, their independent roles in the course of this disease have not been determined. We assessed the association between the course of Graves' disease and psychosocial factors by using multivariate analysis. METHODS We investigated the association between the short-term outcome of Graves' disease (assessed 12 months after the beginning of antithyroid drug therapy) and stressful life events, daily hassles, smoking, drinking habits, coping skills, and social support (before and 6 months after beginning therapy) in 230 patients (182 women and 48 men) with newly diagnosed Graves' disease, using a logistic regression model. RESULTS After adjustment for smoking, coping skills, and thyroid function, daily hassles scores in women at 6 months after beginning therapy were significantly associated with a hyperthyroid state 12 months after beginning therapy. The relative risk was 3.9 for women with higher daily hassles scores compared with women with lower daily hassles scores (95% confidence interval, 1.1 to 13.2; p < .05). Smoking was not significantly associated with a hyperthyroid state 12 months after beginning therapy in either women or men. CONCLUSIONS Chronic psychological stress is associated with the course of Graves' disease in women.