Background: Debate persists regarding the efficacy of prophylactic mesh insertion (PMI) at index permanent stoma creation to reduce the rate of parastomal hernia (PSH). This meta-analysis aimed to appraise all the latest evidence from newly published randomized controlled trials (RCTs) on PMI for PSH prevention. Methods: PubMed, EMBASE, and Cochrane databases were searched for relevant articles from inception until November 2020. All RCTs that reported on PMI at end colostomy creation with ≥ 12 months follow-up were included. The primary objective was the rate of clinical and radiological PSH while secondary objectives included number of PSH requiring repair and stoma (or mesh)-related complications. Random effects models were used to calculate pooled effect size estimates. Sensitivity analyses were also performed. Results: Eleven RCTs were included capturing 1097 patients. The mean (SD) age was 67.9 (±9.4) years. On random effects analysis, prophylactic mesh appeared to reduce the rate of both clinical (OR = 0.27, 95% CI = 0.12 to 0.61, p = 0.002) and radiological (OR = 0.39, 95% CI = 0.24 to 0.65, p = 0.0002) PSH. However, there was no difference in number of PSH requiring repair or stoma-related complications. On sensitivity analysis, when focusing on low-risk of bias studies, the benefit of prophylactic mesh in the retrorectus space was lost for both clinical (OR = 0.97, 95% CI = 0.62 to 1.51, p = 0.89) and radiological PSH (OR = 0.74, 95% CI = 0.46 to 1.18, p = 0.20). Conclusion: PMI may reduce the rate of subsequent PSH. However, further studies are required to confirm these findings and to establish the optimal mesh position and shape before definite recommendations can be made.