Absorbable antibacterial envelopes (AAEs) are currently recommended in patients undergoing a transvenous ICD implantation in cases at high-risk of infection, who are indeed now preferably implanted with a subcutaneous ICD (S-ICD), whenever possible. Nevertheless, experiences using a combined approach with S-ICD and AAE have not been reported, therefore, aim of our study was to evaluate this strategy in patients at very high-risk of infection. Sixteen patients were implanted with the S-ICD+AAE using our combined approach, restricted to patients who would fit our decisional flow algorithm. Despite a very high-risk, only a single pocket infection was observed over the entire follow-up that was managed conservatively and solved 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 safe, feasible and may offer a true clinical benefit in specific clinical settings.