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Objectives To evaluate the feasibility and safety of a novel multi-electrode pulmonary vein ablation catheter (PVAC) combining circular mapping and duty-cycled multi-electrode radiofrequency (RF) energy delivery, and guided by three-dimensional rotational angiography (3D-RTA) for atrial fibrillation (AF). Methods 47 patients (aged 62±11 years) with symptomatic AF 32 cases for paroxysmal AF and 15 cases for persistent AF were enrolled to undergo pulmonary vein isolation (PVI) with PVAC guided by 3D-RTA. Results Mean total procedural time was 126.4±29.5 min (123.7±15.7 min for the paroxysmal AF patients and 132.0±36.6 min for the persistent AF patients, p>0.05); mean fluoroscopy time was 30.3±11.3 min (29.4±9.8 min for the paroxysmal AF patients and 32.3±14.2 min for the persistent AF patients, p>0.05); mean PVAC ablation time was 21.6±7.7 min (20.5±6.0 min for the paroxysmal AF patients and 24.0±10.4 min for the persistent AF patients, p>0.05). A total of 172 PVs (172/183, 94.0%) were completely isolated. Two cases of mild pericardial effusion were detected on the first postprocedural day and absorbed in a week. No incidence of PV stenosis was observed during the follow-up. At follow-up (mean 8±5 months, range 3–22 months), 32 (68.1%) patients reported significantly improved symptoms or were entirely asymptomatic. 29 of 47 (61.7%) patients were free from AF. Conclusions The novel technology of the PVAC catheter using duty-cycled bipolar and unipolar RF energy and guided by 3D-RTA suggests a feasible, safe, and promising alternative to conventional point-by-point ablation.