BACKGROUND: Noncardiovascular (non-CV) comorbidities may contribute to hospitalizations in patients with heart failure (HF). We examined the incidence of mortality following hospitalization for cardiovascular (CV) versus non-CV reasons in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program. METHODS AND RESULTS: First hospitalizations for CV or non-CV reasons during the CHARM trial (N=7599) were related to subsequent risk of all-cause death using time-updated proportional hazards models. Over median 37.7 month follow-up, 2816 subjects (37.1%) were not hospitalized, 2893 (38.1%) were first hospitalized for CV reasons, and 1890 (24.9%) for non-CV reasons. The death rate (per 100 patient-years) among those not hospitalized was 2.8 compared with 17.8 after CV and 16.5 after non-CV hospitalization (both P<0.001 versus not hospitalized). Mortality at 30 days was higher after CV than non-CV hospitalization; however, among 30-day survivors of CV and non-CV hospitalization, rates of subsequent mortality were similar (14.5 versus 14.6 per 100 patient-years; P=0.62). Rates of CV hospitalization were higher for those with ejection fraction (EF) ≤40% than those with EF >40% (P<0.001), but rates of non-CV hospitalization did not vary by EF. Low EF patients had higher risk for mortality than preserved EF patients after any hospitalization, but within each EF subgroup, mortality in 30-day survivors of CV versus non-CV hospitalization was similar. CONCLUSIONS: Non-CV hospitalization is frequent in patients with symptomatic heart failure and associated with risk of subsequent mortality similar to CV hospitalization across the spectrum of EF. These findings may have implications for developing strategies to prevent readmissions. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00634309 (CHARM-Added), NCT00634712 (CHARM-Preserved), NCT00634400 (CHARM-Alternative).