Background—: The rate of implantable cardioverter-defibrillator (ICD) infections has been increasing faster than that of implantation. We sought to determine the rate and predictors of ICD infection in a large cohort of Medicare patients. Methods and Results—: Cases submitted to the ICD Registry from 2006 to 2009 were matched to Medicare fee-for-service claims data using indirect patient identifiers. ICD infections occurring within 6 months of hospital discharge after implantation were identified by ICD-9 codes. Logistic regression was used to examine factors associated with risk of ICD infection. Of 200 909 implants, 3390 patients (1.7%) developed an ICD infection. The infection rate was 1.4%, 1.5%, and 2.0% for single, dual, and biventricular ICDs, respectively ( P <0.001). Generator replacement had a higher rate compared with initial implant (1.9% versus 1.6%, P <0.001). The factors associated with infection were adverse event during implant requiring reintervention (odds ratio [OR], 2.692; 95% confidence interval [CI], 2.304–3.145), previous valvular surgery (OR, 1.525; 95% CI, 1.375–1.692), reimplantation for device upgrade, malfunction, or manufacturer advisory (OR, 1.354; 95% CI, 1.196–1.533), renal failure on dialysis (OR, 1.342; 95% CI, 1.123–1.604), chronic lung disease (OR, 1.215; 95% CI, 1.125–1.312), cerebrovascular disease (OR, 1.172; 95% CI, 1.076–1.276), and warfarin (OR, 1.155; 95% CI, 1.060–1.257). Conclusions—: Patients who developed an ICD infection were more likely to have had peri-ICD implant complications requiring early reintervention, previous valve surgery, device replacement for reasons other than battery depletion, and increased comorbidity burden. Efforts should be made to carefully consider when to reenter the pocket at any time other than battery replacement.