Absorbable antibacterial envelopes (AAEs) are currently recommended in patients undergoing a transvenous ICD implantation in cases at high risk of infection, who are now preferably implanted with a subcutaneous ICD (S-ICD). Nevertheless, experiences using a combined approach with S-ICD and AAE have not been reported. The aim of our study was to evaluate this strategy in patients at very high risk of infection. Twenty-five patients were implanted with the S-ICD+AAE using our combined approach, restricted to patients who would fit our decisional flow algorithm identifying very high-risk patients. Patients were followed up 1 month after discharge and every 6 months thereafter. Complications were defined as device-related events requiring medical or surgical intervention for resolution and/or device reprogramming. Twenty-five patients (92% males, mean age 58.5±14.1 years) were implanted with the S-ICD device and the AAE using our combined approach. The most common high-infective risk factors were diabetes requiring insulin treatment (80%) and CKD requiring hemodialysis (48%), with 7 (28%) patients presenting with more than 2 risk factors. A single mild early post-operative hematoma was observed that was managed conservatively with a spontaneous resolution. Despite a very high-risk cohort, only a single late pocket infection was detected and solved conservatively with antibiotic therapy. The preliminary data of this proof-of-concept study show how a combined deployment of AAE and S-ICD in selected patients at very high risk of infection is a safe and feasible technique and may offer a reliable treatment option in specific and selected clinical settings.