Background: Incisional hernia is a frequent complication after abdominal surgery. The aim of this study was to assess the efficacy of prophylactic mesh reinforcement (PMR) after midline laparotomy in reducing the incidence of incisional hernia.Methods: A meta-analysis was conducted following PRISMA guidelines. The primary outcome was the incidence of incisional hernia after follow-up of at least 12 months. Secondary outcomes were postoperative complications. Only RCTs were included. A random-effects model was used for the meta-analysis, and trial sequential analysis was conducted.Results: Twelve RCTs were included, comprising 1815 patients. The incidence of incisional hernia was significantly lower after PMR compared with sutured closure (risk ratio (RR) 0⋅35, 95 per cent c.i. 0⋅21 to 0⋅57; P < 0⋅001). Both onlay (RR 0⋅26, 0⋅11 to 0⋅67; P = 0⋅005) and retromuscular (RR 0⋅28, 0⋅10 to 0⋅82; P = 0⋅02) PMR led to a significant reduction in the rate of incisional hernia. The occurrence of seroma was higher in patients who had onlay PMR (RR 2⋅23, 1⋅10 to 4⋅52; P = 0⋅03). PMR did not result in an increased rate of surgical-site infection.Conclusion: PMR of a midline laparotomy using an onlay or retromuscular technique leads to a significant reduction in the rate of incisional hernia in high-risk patients. Individual risk factors should be taken into account to select patients who will benefit most.[Correction added on 19 February 2020, after first online publication: J. García Alamino has been amended to J. M. Garcia-Alamino]