Open, emergency abdominal surgery is associated with a high incidence of fascial dehiscence and incisional hernia. Implantation of biologic meshes potentially reinforces the abdominal wall and therefore decreases such complications. The aim of this prospective randomized study was to compare the outcome after prophylactic intraperitoneal implantation of a biologic Strattice mesh (Allergan, Dublin, Ireland) with standard abdominal closure in patients undergoing emergency abdominal surgery. A two-arm randomized clinical trial was performed in patients undergoing emergency abdominal surgery at Bern University Hospital, University of Bern, Switzerland, from April 2016 to March 2019. Patients were randomly assigned to prophylactic implantation of a biological intraperitoneal mesh using Strattice, Allergan (mesh group), or standard abdominal closure using a single, continuous running suture (no-mesh group). Because of safety concerns, patient enrollment was closed prematurely. Eligibility for inclusion was assessed in 61 patients. A total of 48 patients were randomized (21 in the mesh group, 28 in the no-mesh group). No differences in baseline characteristics were found. Abdominal wall complications requiring reoperations were more frequent in the mesh group compared to the no-mesh group (5 [83.3%] of 13 vs. 1 [14.3%] of 13 patients, p = 0.026). Mesh-associated abdominal wall complications included nonintegration of the mesh into the abdominal wall, dissolution of the mesh, and mesh-related infections. In patients undergoing emergency abdominal surgery, intraperitoneal biologic Strattice mesh implantation is associated with significantly more frequent abdominal wall complications requiring reoperation. Therefore, the use of such meshes cannot be recommended in the contaminated environment of emergency abdominal surgery. Therapeutic, level I.