BACKGROUND The subcutaneous implantable cardioverter-defibrillator (S-ICD) provides an alternative to the transvenous implantable cardioverter-defibrillator (TV-ICD). Patients undergoing TV-ICD explantation may be eligible for reimplantation with an S-ICD; however, information on safety outcomes in this complex population is limited. OBJECTIVE This analysis was designed to provide outcome and safety data from S-ICD patients who received their device after TV-ICD explantation. METHODS Patients in the S-ICD IDE Study and EFFORTLESS Registry with a prior TV-ICD explantation, as well as those with no prior implantable cardioverter-defibrillator (ICD), were included. Patients were divided into 3 groups: those implanted with the S-ICD after TV-ICD extraction for system-related infection (n = 75); those implanted after TV-ICD extraction for reasons other than system-related infection (n = 44); and patients with no prior ICD (de novo implantations, n = 747). RESULTS Mean follow-up duration was 651 days, and all-cause mortality was low (3.2%). Patients previously explanted for TV-ICD infection were older (55.5 ± 14.6, 47.8 ± 14.3 and 49.9 ± 17.3 years in the infection, noninfection, and de novo cohorts, respectively; P = .01), were more likely to have received the ICD for secondary prevention (42.7%, 37.2% and 25.6%; P < 0.0001) and had higher percentages of comorbidities, including atrial fibrillation, congestive heart failure, diabetes mellitus, and hypertension, in line with the highest mortality rate (6.7%). Major infection after S-ICD implantation was low in all groups, with no evidence that patients implanted with the S-ICD after TV-ICD explantation for infection were more likely to experience a subsequent reinfection. CONCLUSION The S-ICD is a suitable alternative for TV-ICD patients whose devices are explanted for any reason. Postimplantation risk of infection remains low even in patients whose devices were explanted for prior TV-ICD infection.