BACKGROUND: Despite the obvious benefits, the use of implantable cardioverter defibrillators (ICDs) is associated with serious complications, including infections. In particular, device replacement or revision procedures are associated with an increased risk of infection. OBJECTIVE: The aim of the study was to compare the cardiac device infection rate with and without the use of a gentamycin-collagen sponge (GCS) in patients undergoing device replacement or revision procedures of implanted ICDs. METHODS: A total of 507 consecutive ICD patients from a prospective single-center ICD-registry who underwent elective device replacement, system upgrade or lead revision between 2017 and 4/2024 were analyzed. From September 2020 onwards, a GCS was inserted into the device pocket (GCS group, n = 277). These patients were compared with patients who underwent surgery between 2017 and 8/2020 (control group, n = 230). RESULTS: The baseline characteristics were similar between both groups. The GCS was well tolerated and there were no complications associated with the GCS. The Kaplan-Meier estimated infection rate after one year was 0.7% in the GCS group and 3.9% in the control group (p = 0.005). The use of the GCS was an independent predictor for a lower device infection rate during follow-up (HR 0.23, 95% CI 0.07 - 0.84). CONCLUSION: The additional use of a GCS was associated with a lower incidence of device infections than standard-of-care infection-prevention strategies alone.