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OBJECTIVE: Poststroke depression has been linked to higher mortality after stroke. However, the effect of other mental health conditions on poststroke mortality has not been examined. The objective of this study was to evaluate the effect of poststroke depression and other mental health diagnoses on mortality after ischemic stroke. METHOD: The authors examined a national cohort of veterans hospitalized after an ischemic stroke at any U.S. Department of Veterans Affairs (VA) medical center from 1990 to 1998. Demographic, admission, and all-cause mortality data were abstracted from VA administrative databases. Chronic conditions present at discharge and new poststroke depression and other mental health diagnoses within 3 years after the stroke were identified with ICD-9 codes. Mortality hazard ratios were modeled by using Cox regression models. RESULTS: A total of 51,119 patients hospitalized after an ischemic stroke who survived beyond 30 days afterward were identified; 2,405 (5%) received a diagnosis of depression, and 2,257 (4%) received another mental health diagnosis within 3 years of their stroke. Patients with poststroke depression were younger, more often white, and less likely to be alive at the end of the 3-year follow-up period. Both poststroke depression (hazard ratio=1.13, 95% CI=1.06–1.21) and other mental health diagnoses (hazard ratio=1.13, 95% CI=1.07–1.22) independently increased the hazard for death even after other chronic conditions were controlled. CONCLUSIONS: Despite being younger and having fewer chronic conditions, a higher 3-year mortality risk was seen in patients with poststroke depression and other mental health diagnoses after hospitalization for an ischemic stroke. The biological and psychosocial mechanisms driving this greater risk should be further explored, and the effect of depression treatment on mortality after stroke should be tested.