New-generation drug-eluting stents (DES) represent the current standard of care in patients undergoing percutaneous coronary intervention (PCI). Biodegradable polymer DES (BP-DES) were recently developed to overcome current limitations of newer-generation durable polymer DES (DP-DES) attributed to sustained inflammatory responses induced by permanent polymers. The Orsiro DES (Biotronik AG, Bülach, Switzerland) is a novel thin-strut cobalt-chromium sirolimus-eluting stent with biodegradable polymer that features some of the latest developments in DES technology. Areas covered: This article aims to review the currently available evidence on the clinical performance of the Orsiro BP-DES and its future perspectives. Expert commentary: The Orsiro DES is a recent newer-generation BP-DES that combines a highly deliverable thin-strut cobalt-chromium stent platform and a unique hybrid concept with passive and active coatings designed to enhance tissue biocompatibility. In preclinical and intravascular imaging studies, the Orsiro BP-DES was shown to induce low inflammation and promote very early arterial healing. Recently, large randomized non-inferiority clinical trials have shown similar short- and mid-term efficacy and safety outcomes with Orsiro BP-DES compared with currently established newer-generation DES among all-comers and high-risk subgroups. The potential clinical superiority of Orsiro BP-DES over Xience DP-DES in patients with STEMI is currently investigated in the BIOSTEMI trial (NCT02579031).