Transthoracic device closure (TTDC) is thought to be a promising technology for the repair of ventricular septal defects (VSDs). However, there is considerable controversy regarding the efficacy and safety of TTDC. The present study aimed to compare the benefits and safety of TTDC with those of conventional open-heart surgery (COHS) and analyze the associated factors causing complications, conversion to COHS and reoperation. Electronic database searches were conducted in PubMed, EMBASE, Cochrane Library, Clinicaltrials.gov and several Chinese databases. A total of 5 randomized controlled trials (RCTs), 7 cohort studies, 13 case-control studies, 129 case series and 13 case reports were included. Compared to COHS, TTDC exhibited superior efficacy with a significantly lower risk of post-operative arrhythmia; however, no significant differences in other outcomes were identified. Meta-regression analysis showed that perimembranous VSDs (pmVSDs), a smaller VSD, a smaller occluder, and a median or subxiphoid approach lowered the relative risk of several post-operative complications, conversion to COHS and reoperation. The current evidence indicates that TTDC is associated with a lower risk of post-operative arrhythmia and is not associated with an increased risk of complications. PmVSDs, a smaller VSD and occluder, and a median or subxiphoid approach correlate with better outcomes when using TTDC.