Objective To explore the technique of performing minimally invasive Cox Maze Ⅳ procedure by bipolar clamp through right lateral minithoracotomy for atrial septal defect (ASD) combined with atrial fibrillation (AF) in adults. Methods Thirty-five patients (21 males, 14 females with age ranging from 45 to 73 years) with ASD and persistent or long-standing persistent AF received minimally invasive Cox Maze Ⅳ procedure and ASD closure from August 2012 to April 2016 at Department of Cardiothoracic Surgery, Xinhua Hospital. Diameter of left atrium ranged from 39 to 60 mm and left ventricle ejection fraction (LVEF) ranged from 48% to 62%. Diameter of ASD ranged from 20 to 35 mm. Cox-maze Ⅳ procedure was performed through right minithoracotomy entirely by bipolar radiofrequency clamp. Then, mitral or tricuspid valvuloplasty and surgical ASD closure was performed through right minithoracotomy. Results All patients successfully underwent this minimally invasive surgery. No patient needed conversion to sternotomy. The mean cardiopulmonary bypass time was 120.1±14.1 min. The mean aortic cross-clamp time was 79.5±12.2 min. There was no early death or pacemaker implantation perioperatively. The average length of hospital stay was 10.1±2.7 d. At a mean follow-up of 22.8±12.2 months, sinus rhythm was restored in 32 patients (32/35, 91.4%). Cumulative maintenance of normal sinus rhythm without AF recurrence at 2 years postoperatively was 89.1%±6.0%. Conclusion The minimally invasive Cox Maze Ⅳprocedure performed by bipolar clamp through right minithoracotomy is safe, feasible, and effective for adult patients with ASD combined with AF.