BACKGROUND: Recent observations suggest statin treatment may be associated with lower mortality in heart failure (HF). The SCD-HeFT was a study of 2521 functional class II and III HF patients with left ventricular ejection fractions < or = 35% and ischemic and nonischemic cardiomyopathy followed up for a median of 45.5 months. The study length, size, and degree of background HF, including the use of implantable defibrillator therapy, provide a unique opportunity to evaluate the impact of statin use in HF with mechanistic insights from subgroup analyses. METHODS AND RESULTS: Statin use was reported in 965 (38%) of 2521 patients at baseline and 1187 (47%) at last follow-up. The relationships between statin use, randomization arm, disease category, and functional class and all cause mortality were assessed. Statin use was studied as a time-dependent covariate in a multivariable Cox proportional hazards model, adjusted for imbalances between statin and no-statin groups. Mortality risk was significantly lower in those taking a statin (HR [95% CI], 0.70 [0.58-0.83]). Mortality risk was lower with statin use in all prespecified subgroups: ischemic cardiomyopathy (0.69 [0.56-0.86]), nonischemic cardiomyopathy (0.67 [0.47-0.96]), implantable cardioverter defibrillator (ICD) (0.66 [0.46-0.95], non-ICD (0.71 [0.57-0.87]), New York Heart Association II (0.62 [0.48-0.79]), and New York Heart Association III (0.79 [0.61-1.03]). CONCLUSIONS: Statin use is associated with reduced all-cause mortality in HF patients. Statins appear to benefit patients with nonischemic and ischemic cardiomyopathy similarly. Statin benefits are similar in ICD and non-ICD patients.