Ventricular septal defect (VSD) induced by acute myocardial infarction (AMI) is rare but lethal, with high mortality even after surgical repair. Our aim was to assess the association between the time interval and surgical repair effects in patients with VSD following AMI. From January 2003 to December 2017, 14 patients with VSD induced by AMI received surgical therapy in our department. We retrospectively reviewed the patients' clinical manifestations, surgical methods, and outcomes. According to the time interval from AMI onset and surgery, we divided the patients into two groups: Group 1 (N = 9), more than one week, and Group 2 (N = 5), less than one week. A comparison study was performed, and differences were analyzed. The mean age of the entire group was 65.5±3.3 years, with 78.6% males (11/14). VSDs were anterior apical in 10 (71.4%) and posterior inferior in 4 (28.6%) patients. The average size of the VSD was 15.8±5.8 mm. Compared with Group 1, Group 2 had poorer left ventricular function (LVEF 40.8±10.3% vs. 30.4±2.3%, P = 0.035) and a higher rate of urgent procedures (11.1% vs. 100.0%, P = 0.003). The mortality rate was 14.3% (2/14). Mechanical support was more common in Group 2 than Group 1. No resistant shunt or death was found during follow up. VSD following AMI is safer for more than one week, but surgical treatment is also acceptable for patients requiring urgent surgery due to hemodynamic instability. Mechanical assistive devices can improve the perioperative success rate.