Aims Periprocedural pulmonary vein isolation (PVI) anticoagulation requires balancing between the risk of bleeding and thromboembolism. Intraprocedural anticoagulation is monitored by activated clotting time (ACT) and there are no guidelines which specify an initial unfractionated heparin (UFH) dose. We aimed to assess differences in ACT values and UFH dosage during PVI in patients on different oral anticoagulants. Methods We conducted international, multi-centre, registry-based study. Consecutive patients with atrial fibrillation (AF) undergoing PVI, on uninterrupted anticoagulation therapy, were analysed. Before the transseptal puncture, UFH bolus of 100 U/kg was administered regardless of the anticoagulation drug. Results A total of 873 AF patients were included (median age 61 years, IQR 53-66; female 30%). There were 248, 248, 189, 188 patients on warfarin, dabigatran, rivaroxaban, and apixaban, respectively. Mean initial ACT was 257±50 sec, overall procedural ACT 295±45 sec and total UFH dose 158±60 IU/kg. Patients who were receiving warfarin and dabigatran compared to patients receiving rivaroxaban and apixaban had: (i) significantly higher initial ACT values (262±57 and 270±48 vs. 248±42 and 241±44 sec, p<0.001), (ii) significantly higher ACT throughout PVI (309±46 and 306±44 vs. 282±37 and 272±42 sec, p<0.001), and (iii) needed lower UFH dose during PVI (140±39 and 157±71 vs. 171±52 and 172±70 IU/kg). Conclusion There are significant differences in ACT values and UFH dose during PVI in patients receiving different anticoagulants. Patients on warfarin and dabigatran had higher initial and overall ACT values and needed lower UFH dose to achieve adequate anticoagulation during PVI than patients on rivaroxaban and apixaban.