Objective To investigate surgical strategy for the treatment of muscular ventricular septal defect （MVSD） in infants with multiple ventricular septal defects（VSD）. Methods Clinical data of 46 infants with multiple VSD who underwent surgical repair in Shanghai Children’s Medical Center from January 2010 to April 2012 were retrospectively analyzed. There were 24 males and 22 females with their age of 8±6 months and body weight of 6.1±1.9 kg. All the patients received one-stage surgical repair，among whom MVSD of 10 patients was not found and repaired during the surgery. MVSD was repaired by surgical suture in 19 patients，hybrid repair under direct vision in 12 patients，and hybrid repair via the right ventricle in 5 patients. All the patients were regularly followed up after discharge by chest X-ray，ECG and color Doppler echocardiography to observe the closure of MVSD and the presence of residual shunt. Results All the 46 patients with multiple VSD survived their surgery without perioperative death. Three patients undergoing hybrid repair under direct vision received delayed sternal closure. One patient undergoing hybrid repair under direct vision had postoperative cardiac dysfunction. All the 46 patients were followed up for 1-17 months. Twenty-three patients had residual shunt of varying degrees during follow-up，and most of the MVSD of patients with residual shunt were ＜4 mm，who were receiving further follow-up and evaluation. Conclusion Appropriate surgical strategies can be applied according to specific surgical views during the operation for the treatment of MVSD in infants with multiple VSD，and satisfactory clinical outcomes can be achieved.