Purpose: Anastomotic leakage after small bowel resection in emergency laparotomy is a severe complication. A consensus on the risk factors for anastomotic leakage has not been established, and it is still unclear if peritonitis is a risk factor. This systematic review aimed to evaluate if an entero-entero/entero-colonic anastomosis is safe in patients with peritonitis undergoing abdominal acute care surgery. Methods: A systematic literature review based on PRISMA guidelines was performed, searching the databases Pubmed/MEDLINE, Cochrane Library, and Science Direct for studies of anastomosis in peritonitis. Patients with an anastomosis after non-planned small bowel resection (ischemia, perforation, or strangulation), including secondary peritonitis, were included. Elective laparotomies and colo-colonic anastomoses were excluded. Due to the etiology, traumatic perforation, in-vitro, and animal studies were excluded. Results: This review identified 26 studies of small-bowel anastomosis in peritonitis with a total of 2807 patients. This population included a total of 889 small-bowel/right colonic resections with anastomoses, and 242 enterostomies. All studies, except two, were retrospective reviews or case series. The overall mortality rates were 0–20% and anastomotic leakage rates 0–36%. After performing a risk of bias evaluation there was no basis for conducting a meta-analysis. The quality of evidence was rated as low. Conclusion: There was no evidence to refute performing a primary small-bowel anastomosis in acute laparotomy with peritonitis. There is currently insufficient evidence to label peritonitis as a risk factor for anastomotic leakage in acute care laparotomy with small-bowel resection. Trial registration: The review was registered with the PROSPERO register of systematic reviews on 14/07/2020 with the ID: CRD42020168670.