From the patient's perspective, a ventral hernia (VH) can cause pain, adversely affect function, increase size, cosmetically distort the abdomen, and incarcerate/strangulate abdominal contents. The only known "cure" for a VH is surgical repair. The aim of this study was to review systematically the published randomized controlled trials (RCTs) of the surgical care of VH. A search of the Ovid, MEDLINE, EMBASE, and Cochrane databases was performed to obtain reports of RCTs on the use of mesh reinforcement in abdominal wall hernia repair. The outcomes assessed were hernia recurrence and surgical site infection (SSI). The overall quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). When feasible, based on assessment of heterogeneity, data were pooled and analyzed in a meta-analysis. Of the 10,349 titles screened, 25 articles (23 studies) met the search criteria. Evidence indicates that mesh reinforcement in clean cases can decrease hernia recurrence (number needed to treat = 7.9) but increase risk of SSI (number needed to harm = 27.8). Placing mesh in the sublay position (as opposed to the onlay or underlay position) may decrease the risk of hernia recurrence and SSI. Mesh reinforcement is recommended for all VH repairs in a clean case (high grade of evidence). Sublay mesh location may result in fewer recurrences and SSIs than onlay or inlay placement, but further study is needed to confirm this hypothesis (moderate grade of evidence).