BACKGROUND: Implantable cardioverter-defibrillators (ICDs) have a role in preventing cardiac arrest in patients at risk for life-threatening ventricular arrhythmias. PURPOSE: To compare ICD therapy with conventional care for the primary prevention of death of various causes in adults with ischemic or nonischemic cardiomyopathy. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, and EMBASE databases, as well as several Web sites, from 1 April 1976 through 31 March 2017. STUDY SELECTION: Randomized controlled trials, published in any language, comparing ICD therapy with conventional care and reporting mortality outcomes (all-cause, sudden, any cardiac, or noncardiac) in the primary prevention setting. DATA EXTRACTION: 2 independent investigators extracted study data and assessed risk of bias. DATA SYNTHESIS: Included were 11 trials involving 8716 patients: 4 (1781 patients) addressed nonischemic cardiomyopathy, 6 (4414 patients) ischemic cardiomyopathy, and 1 (2521 patients) both types of cardiomyopathy. Mean follow-up was 3.2 years. An overall reduction in all-cause mortality, from 28.26% with conventional care to 21.37% with ICD therapy (hazard ratio [HR], 0.81 [95% CI, 0.70 to 0.94]; P = 0.043), was found. The magnitude of reduction was similar in the cohorts with nonischemic (HR, 0.81 [CI, 0.72 to 0.91]) and ischemic (HR, 0.82 [CI, 0.63 to 1.06]) disease, although the latter estimate did not reach statistical significance. The rate of sudden death fell from 12.15% with conventional care to 4.39% with ICD therapy (HR, 0.41 [CI, 0.30 to 0.56]), with a similar magnitude of reduction in patients with ischemic (HR, 0.39 [CI, 0.23 to 0.68]) and those with nonischemic disease (HR, 0.44 [CI, 0.17 to 1.12]). Noncardiac and any cardiac deaths did not differ significantly by treatment. LIMITATION: Heterogeneous timing of ICD placement; heterogeneous pharmacologic and resynchronization co-interventions; trials conducted in different eras; adverse events and complications not reviewed. CONCLUSION: Overall, primary prevention with ICD therapy versus conventional care reduced the incidence of sudden and all-cause death. PRIMARY FUNDING SOURCE: None.