Objective To evaluate the safety and efficacy of biatrial Cox Maze Ⅳ cryoablation for concomitant atrial fibrillation (AF) during minimally invasive valve surgery. Methods A total of 47 patients (26 males, 21 females, age of 42-69 years) with mitral valve disease and long-standing persistent AF received minimally invasive biatrial Cox Maze Ⅳ cryoablation procedure combined with mitral valve surgery through right minithoracotomy from January 2014 to September 2015. The etiology of mitral valve disease was rheumatic (n=31) and degenerative (n=16). AF duration ranged from 2 to 11 years. Diameter of the left atrium ranged from 43 to 60 mm. Concomitant biatrial Cox Maze Ⅳ cryoablation procedure was performed through right lateral minithoracotomy. Results All 47 patients successfully underwent this minimally invasive concomitant biatrial Cox Maze Ⅳ cryoablation procedure and valve surgery. No patient needed conversion to sternotomy during the surgery. The mean cardiopulmonary bypass time, aortic cross-clamp time and cryoablation time was 95-146 (120.3±12.3) min, 82-115 (93.3±7.7) min and 32-48 (38.6±4.5) min, respectively. There was no death perioperatively. The average postoperative length of hospital stay was 5-16 (7.9±1.9) d. At discharge, 44 patients (44/47, 93.6%) maintained sinus rhythm. At a mean follow-up of 6-26 (14.4±5.4) months, sinus rhythm was maintained in 41 patients (41/47, 87.2%). Cumulative maintenance rate of normal sinus rhythm without AF recurrence at one year postoperatively was 86.3%±5.8%. Conclusion Biatrial Cox Maze Ⅳ cryoablation procedure is safe, feasible and effective for AF during concomitant minimally invasive valve surgery.