BACKGROUND: Aortic valve prolapse (AVP) and aortic regurgitation (AR) can develop in a subset of patients with ventricular septal defect (VSD). The incidence and progression of AVP and AR with VSD at long-term follow up was evaluated. METHODS: The records of 2,275 patients with isolated VSD who had been diagnosed using echocardiography at the present authors' institution between 1988 and 2014 were reviewed. RESULTS: AVP was detected in 178 patients (7.8%), using echocardiography. Of 178 patients with AVP, AR was detected in 124 (AR incidence 5.4%). A total of 142 patients was followed medically during a median of 10 years after AVP had appeared. Initially, no AR was noted in 66 of these patients, trivial AR in 41, mild AR in 30, moderate in three, and severe in two. Trivial AR developed in 20 and mild in eight of 66 patients who had no AR. In 18 of 61 patients (29.5%), trivial AR progressed to mild during a median of 3.6 years, and in five of 18 patients (27.7%) mild AR progressed to moderate during a median of 2.3 years. Postoperatively, AR improved in 17 patients, remained unchanged in 12, and worsened in four at between two months and 16.5 years of follow up (median 6.6 years). CONCLUSIONS: Frequent (six-month) echocardiographic evaluation in patients with perimembraneous or muscular outlet VSD after AVP and AR development may be useful. In addition, surgical intervention in patients with perimembraneous or muscular outlet VSD, AVP and mild AR may prevent the worsening of AR.