There is no consensus on the ideal location for mesh placement in open ventral hernia repair (OVHR). We aim to identify the mesh location associated with the lowest rate of recurrence following OVHR using a systematic review and meta-analysis. A search was performed for studies comparing at least two of four locations for mesh placement during OVHR (onlay, inlay, sublay, and underlay). Outcomes assessed were hernia recurrence and surgical site infection (SSI). Pairwise meta-analysis was performed to compare all direct treatment of mesh locations. A multiple treatment meta-analysis was performed to compare all mesh locations in the Bayesian framework. Sensitivity analyses were planned for the following: studies with a low risk of bias, incisional hernias, by hernia size, and by mesh type (synthetic or biologic). Twenty-one studies were identified (n = 5,891). Sublay placement of mesh was associated with the lowest risk for recurrence [OR 0.218 (95% CI 0.06-0.47)] and was the best of the four treatment modalities assessed [Prob (best) = 94.2%]. Sublay was also associated with the lowest risk for SSI [OR 0.449 (95% CI 0.12-1.16)] and was the best of the 4 treatment modalities assessed [Prob (best) = 77.3%]. When only assessing studies at low risk of bias, of incisional hernias, and using synthetic mesh, the probability that sublay had the lowest rate of recurrence and SSI was high. Sublay mesh location has lower complication rates than other mesh locations. While additional randomized controlled trials are needed to validate these findings, this network meta-analysis suggests the probability of sublay being the best location for mesh placement is high.