Background: Limited information is available on the comparative efficacy and safety of different stent platforms in patients at high bleeding risk undergoing an abbreviated dual antiplatelet therapy duration after percutaneous coronary intervention (PCI). The aim of this study was to compare the safety and effectiveness of the biodegradable-polymer sirolimus-eluting stent with the durable-polymer zotarolimus-eluting stent in patients at high bleeding risk receiving 1 month of dual antiplatelet therapy after PCI., Methods: The Bioflow-DAPT Study is an international, randomized, open-label trial conducted at 52 interventional cardiology hospitals in 18 countries from February 24, 2020, through September 20, 2021. Patients with a clinical indication to PCI because of acute or chronic coronary syndrome who fulfilled 1 or more criteria for high bleeding risk were eligible for enrollment. Patients were randomized to receive either biodegradable-polymer sirolimus-eluting stents or durable-polymer, slow-release zotarolimus-eluting stents after successful lesion preparation, followed by 1 month of dual antiplatelet therapy and thereafter single antiplatelet therapy. The primary outcome was the composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year, and was powered for noninferiority, with an absolute margin of 4.1% at 1-sided 5% alpha., Results: A total of 1948 patients at high bleeding risk were randomly assigned (1:1) to receive biodegradable-polymer sirolimus-eluting stents (969 patients) or durable-polymer zotarolimus-eluting stents (979 patients). At 1 year, the primary outcome was observed in 33 of 969 patients (3.6%) in the biodegradable-polymer sirolimus-eluting stent group and in 32 of 979 patients (3.4%) in the durable-polymer zotarolimus-eluting stent group (risk difference, 0.2 percentage points; upper boundary of the 1-sided 95% CI, 1.8; upper boundary of the 1-sided 97.5% CI, 2.1; P <0.0001 for noninferiority for both tests)., Conclusions: Among patients at high risk for bleeding who received 1 month of dual antiplatelet therapy after PCI, the use of biodegradable-polymer sirolimus-eluting stents was noninferior to the use of durable-polymer zotarolimus-eluting stents with regard to the composite of death from cardiac causes, myocardial infarction, or stent thrombosis., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04137510., Competing Interests: Disclosures Dr Valgimigli reports grants and personal fees from Terumo and personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi Sankyo, Bayer, CoreFLOW, IDORSIA Pharmaceuticals Ltd, Universität Basel, Department Klinische Forschung, Vifor, Bristol Myers Squibb SA, Biotronik, Boston Scientific, Medtronic, Vesalio, Novartis, Chiesi, and PhaseBio. Dr Wlodarczak has no conflicts of interest to report. Dr Tölg reports personal fees for lectures from Biotronik. Dr Merkely reports personal fees from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, CSL Behring, Daiichi Sankyo, Duke Clinical Research Institute, Medtronic, and Novartis, and institutional grants from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo, Duke Clinical Institute, Eli Lilly, Medtronic, Novartis, Terumo, and VIFOR Pharma. Dr Kelbæk has no conflicts of interest to report. Dr Legutko reports lecture fees from Abiomed, AstraZeneca, Berlin Chemie-Menarini, Abbott, Bayer AG, Ely Lilly, Medtronic, MSD, Philips-Volcano, Procardia, Sanofi, and Novartis; meeting or travel fees from Abbott, Boston, Medtronic, and Abiomed; and data safety monitoring board or advisory board fees from AstraZeneca, Berlin Chemie-Menarini, Abbott, Sanofi, Gedeon Richte, Hemolens Diagnostics, Novartis, and Ferrer. Dr Galli reports consulting fees from BIOACADEMY and lecture fees from PCR. Dr Godin reports lecture fees from B. Braun, Medtronic, and Edwards, and data safety monitoring board or advisory board fees from Terumo and Microport. Dr Toth reports grants and personal fees from Terumo, Abbott Vascular, Biotronik, and Medtronic. Dr Lhermusier reports consulting fees from Abbott and meeting or travel fees from Medtronic. Dr Honton reports consulting fees from Medtronic, Shockwave, Terumo, and Microport; lecture fees from Shockwave, Medtronic, and Boston; and data safety monitoring board or advisory board fees from Microport, Terumo, and Medtronic. Dr Dietrich reports educational event fees to his institution from Cordis. Drs. Stammen and Ferdinande have no conflicts of interest to report. Dr Silvain reports consulting fees from AstraZeneca, Bayer Health Care SAS, CSL Behring SA, Sanofi-Aventis France, and Zoll, and stock options without payment at 4P-Pharma. Dr Capodanno reports honoraria fees from Biotronik and honoraria fees to his institution from Medtronic. Dr Cayla reports personal consulting fees from Edwards, Medtronic, and Microport CRM, and personal honoraria fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol-Myers Squibb, Edwards, Microport, Medtronic, Pfizer, and Sanofi-Aventis.