Background: Identification of patients with nonischemic cardiomyopathy who may benefit from prophylactic implantation of a cardioverter-defibrillator. We hypothesized that periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity, could be used to identify patients who will benefit from prophylactic implantable cardioverter defibrillator (ICD) implantation. Methods: We performed a post hoc analysis of DANISH (Danish ICD Study in Patients With Dilated Cardiomyopathy), in which patients with nonischemic cardiomyopathy, left ventricular ejection fraction (LVEF) ≤35%, and elevated NT-proBNP (N-terminal probrain natriuretic peptides) were randomized to ICD implantation or control group. Patients were included in the PRD substudy if they had a 24-hour Holter monitor recording at baseline with technically acceptable ECG signals during the night hours (00:00–06:00). PRD was assessed using wavelet analysis according to previously validated methods. The primary end point was all-cause mortality. Cox regression models were adjusted for age, sex, NT-proBNP, estimated glomerular filtration rate, LVEF, atrial fibrillation, ventricular pacing, diabetes, cardiac resynchronization therapy, and mean heart rate. We proposed PRD ≥10 deg ² as an exploratory cut-off value for ICD implantation. Results: A total of 748 of the 1116 patients in DANISH qualified for the PRD substudy. During a mean follow-up period of 5.1±2.0 years, 82 of 385 patients died in the ICD group and 85 of 363 patients died in the control group ( P =0.40). In Cox regression analysis, PRD was independently associated with mortality (hazard ratio [HR], 1.28 [95% CI, 1.09–1.50] per SD increase; P =0.003). PRD was significantly associated with mortality in the control group (HR, 1.51 [95% CI, 1.25–1.81]; P <0.001) but not in the ICD group (HR, 1.04 [95% CI, 0.83–1.54]; P =0.71). There was a significant interaction between PRD and the effect of ICD implantation on mortality ( P =0.008), with patients with higher PRD having greater benefit in terms of mortality reduction. ICD implantation was associated with an absolute mortality reduction of 17.5% in the 280 patients with PRD ≥10 deg ² (HR, 0.54 [95% CI, 0.34–0.84]; P =0.006; number needed to treat=6), but not in the 468 patients with PRD <10 deg ² (HR, 1.17 [95% CI, 0.77–1.78]; P =0.46; P for interaction=0.01). Conclusions: Increased PRD identified patients with nonischemic cardiomyopathy in whom prophylactic ICD implantation led to significant mortality reduction.