Abstract Background Subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy is expanding rapidly. However, there are few data on the S-ICD replacement procedure. Objective The aim of this analysis was to describe the procedure and outcome of S-ICD replacement in clinical practice. Methods From 2013 to 2022, consecutive patients undergoing de-novo implantation of an S-ICD were enrolled at 66 Italian centers of the Rhythm Detect Registry. We analyzed consecutive patients who required S-ICD replacement. Results 319 S-ICD generators (49 Cameron, 270 Emblem) were replaced for battery depletion. All the procedures were performed in electrophysiology laboratories, by one or two expert operators. In 118 (37%) cases, the replacement was performed as outpatient procedure. The procedure was performed under local anesthesia with or without conscious sedation in 297 patients (93%). The previous S-ICD generator was in an intermuscular pocket in 195 (61%) patients, and in a subcutaneous pocket in the remaining 124 (39%). 39 (31%) generators were shifted from subcutaneous to intermuscular pocket, and their PRAETORIAN score improved from 43±20 to 34±13 (p=0.007). In most cases (308 (97%)), the defibrillation test was not performed after replacement, but the overall PRAETORIAN score was very low (37±28). The S-ICD system was successfully replaced in all patients and no complications were reported; the procedure duration was 39±16 min and was comparable in the case of generator re-implanted in the same pocket or in case of shift to a new pocket. Conclusions S-ICD replacement was safe and easy to perform, with no peri-operative complications. In clinical practice the replacement procedure is often an opportunity to optimize the position of the generator