BACKGROUND: The benefit of continuing oral anticoagulation (OAC) after catheter ablation (CA) for atrial fibrillation (AF) in patients with a high risk of stroke remains unclear. The Safeness or Threat Of Pausing-Oral anticoagulant therapy After Catheter ablation for atrial fibrillation study (STOP-OAC study) aimed to investigate the safety and efficacy of OAC discontinuation after CA for AF in patients with CHADS2 score ≥2. METHODS: We enrolled 1655 consecutive patients with AF with CHADS2 score ≥2 (mean CHADS2 of 2.4 and CHA2DS2-VASc of 3.8) who underwent first-time CA at 8 institutions in Japan from April 2021 to March 2024. The main analysis was the landmark analysis at 240 days after CA compared between the 2 groups either on or off OAC at 240 days. RESULTS: There were 327 patients who had stopped OAC at 240 days (off-OAC group), and 1241 patients who continued OAC at 240 days (on-OAC group). Patients in the off-OAC group compared with those in the on-OAC group less often had nonparoxysmal AF (43.1% and 54.3%), and history of ischemic stroke (7.7% and 23.4%) with lower CHADS2 score (2.2±0.5 and 2.4±0.6). The incidence of ischemic stroke beyond 240 days was not different between the 2 groups (0.4% and 0.5% per patient-year, P=0.21), whereas the incidence of major or clinically relevant nonmajor bleeding beyond 240 days was significantly lower in the off-OAC group than in the on-OAC group (0.4% and 1.7% per patient-year, P<0.001). CONCLUSIONS: The STOP-OAC study provides real-world evidence supporting the safety and efficacy of early OAC discontinuation after CA of AF in selected patients with CHADS2 score ≥2.