Objective: In March 2004 the U.S. Food and Drug Administration (FDA) warned physicians and patients regarding increased risk of suicide with 10 newer antidepressant drugs. Available data leave considerable uncertainty regarding actual risk of suicide attempt and death by suicide during antidepressant treatment. The authors used population-based data to evaluate the risk of suicide death and serious suicide attempt in relation to initiation of antidepressant treatment., Method: Computerized health plan records were used to identify 65,103 patients with 82,285 episodes of antidepressant treatment between Jan. 1, 1992, and June 30, 2003. Death by suicide was identified by using state and national death certificate data. Serious suicide attempt (suicide attempt leading to hospitalization) was identified by using hospital discharge data., Results: In the 6 months after the index prescription of antidepressant treatment, 31 suicide deaths (40 per 100,000 treatment episodes) and 76 serious suicide attempts (93 per 100,000) were identified in the study group. The risk of suicide attempt was 314 per 100,000 in children and adolescents, compared to 78 per 100,000 in adults. The risk of death by suicide was not significantly higher in the month after starting medication than in subsequent months. The risk of suicide attempt was highest in the month before starting antidepressant treatment and declined progressively after starting medication. When the 10 newer antidepressants included in the FDA advisory were compared to older drugs, an increase in risk after starting treatment was seen only for the older drugs., Conclusions: The risk of suicide during acute-phase antidepressant treatment is approximately one in 3,000 treatment episodes, and risk of serious suicide attempt is approximately one in 1,000. Available data do not indicate a significant increase in risk of suicide or serious suicide attempt after starting treatment with newer antidepressant drugs.