BACKGROUND: Recent reports have provided evidence that bridging therapy with low-molecular-weight heparin (LMWH) may increase bleeding complications in patients with atrial fibrillation (AF) on oral anticoagulation undergoing percutaneous coronary intervention (PCI). We sought to assess mid-term bleeding and thromboembolic events in patients from the AFCAS registry discharged on triple therapy (TT). METHODS: AFCAS is a multicenter, prospective registry enrolling patients with AF undergoing PCI. The primary endpoints were: 1) bleeding complications as defined by the bleeding academic research criteria (BARC); 2) a composite of cardiac and cerebrovascular events (MACCE) at 3 and 12 month follow-ups. RESULTS: Altogether 663 out of 929 consecutive patients were discharged on TT, either on oral vitamin K antagonist (VKA-TT) (n=498) or bridging LMWH-TT (n=165). Patients on LMWH-TT had more often diabetes, heart failure, and hypertension compared to those on VKA-TT. The rates of major bleeding events (BARC≥3) (11.5% vs. 6.0%, p=0.03) as well as MACCE (11.5% vs. 5.0%, p=0.006) were higher in the LMWH-TT group compared to VKA-TT group at 3 months follow-up. In a Cox multivariate regression model and propensity-score matched analysis LMWH-TT increased the risk for major BARC bleeding events at 3 and 12 month follow-ups. CONCLUSIONS: In this large, prospective, real-world population of patients with AF undergoing PCI patients discharged on LMWH-TT had a significantly higher risk for major bleeds in comparison to patients discharged on VKA-TT. LMWH-bridging therapy appeared harmful in this subset of patient on oral anticoagulation.