Aim To observe the level of plasma N-terminal pro-brain natriuretic peptide （NT-proBNP） and heart function in children with ventricular septal defect （VSD） after interventional therapy combined alprostadil injection. Methods A total of 120 patients with VSD for cardiac catheter occlusion were enrolled in this study. All the patients were randomized to alprostadil group （n60） and control group （n60）. Levels of plasma NT-proBNP were measured before and the third day and sixth month after cardiac catheterization, respectively. Before and the seventh day and sixth month after cardiac catheterization, the parameters of left ventricular end diastolic diameter （LVEDD）, left ventricular end systolic diameter （LVESD）, left ventricular end systolic volume （LVESV）, left ventricular end diastolic volume （LVEDV） and left ventricular ejection fraction （LVEF） were measured by echocardiography. Results The parameters of LVEDD, LVESD, LVESV and LVEDV in the sixth month after catheterization were decreased significantly as compared to those before catheterization in the two groups （P<0.05, respectively）, while those in the alprostadil group were more decreased as compared with the control group （P<0.05）.There was no difference in plasma NT-proBNP level between control group and alprostadil group before catheterization （P>0.05）. In the sixth month after catheterization, plasma NT-proBNP level decreased significantly as compared to that before catheterization in the two groups （P<0.01, respectively）, while that in the alprostadil group were more decreased as compared with the control group （P<0.01）. Conclusions Alprostadil injection combined interventional therapy can further reduce the level of plasma NT-proBNP and improve heart function in the children with VSD.