Objective To compare the effects of transthoracic device closure and surgical closure on ventricular septal defect systemically. Methods A systematic literature search was conducted using the PubMed, EMbase, The Cochrane Library, VIP, CNKI, CBM, Chinese Clinical Trial Register, ClinicalTrials. gov and Wanfang Database up to July 31, 2016. Quality was assessed and data of included articles were extracted. The meta-analysis was conducted using RevMan 5.0 and Stata 14.0 software. Results Eleven studies were identified, including 5 RCTs and 6 cohort studies involving 2 504 patients. For success rate, there was no statistical difference between the transthoracic closure group and the surgical closure group in RCT (RR=0.99, 95%CI 0.96 to 1.03, P=0.70); the success rate in the transthoracic closure group was lower than that in the surgical closure group in the cohort study (OR=0.21, 95%CI 0.08 to 0.55, P=0.002). Both results of RCTs and cohort studies showed that compared with surgical closure, transthoracic device closure reduced duration of the operation (RCT MD=–79.38, 95%CI –95.00 to –63.76, P<0.000 01; cohort studyMD=–66.26, 95%CI –71.20 to –61.31, P<0.000 01) and hospital stay (RCTMD=–2.10, 95%CI –2.65 to –1.55, P<0.000 01; cohort studyMD=–3.99, 95%CI –6.03 to –1.94, P=0.000 1), and the patients with blood transfusion (RCT RR= 0.04, 95%CI 0.01 to 0.11, P<0.000 01; cohort studyOR=0.01, 95%CI 0.00 to 0.13, P=0.001). In the transthoracic closure group the risk of postoperative arrhythmia reduced (RCT RR=0.20, 95%CI 0.13 to 0.32, P<0.000 01; cohort studyOR=0.46, 95%CI 0.31 to 0.67, P<0.000 1). In the transthoracic closure group a higher postoperative valvular regurgitation risk in RCT induced (RR=1.45, 95%CI 1.07 to 1.96, P=0.02) and the rate of postoperative valvular regurgitation in cohort study reduced (OR=0.43, 95%CI 0.20 to 0.92, P=0.03). However, there was no statistical difference in postoperative residual shunt (RCT RR=0.96, 95%CI 0.57 to 1.62, P=0.89; cohort study OR=0.52, 95%CI 0.12 to 2.25, P=0.38). Conclusion Transthoracic device closure can shorten duration of the operation, hospital stay and reduce the patients with blood transfusion and post- and intraoperative arrhythmia risk. Therefore, transthoracic device closure may be a better approach for some ventricular septal defect patients.