It is relevant in modern surgery to clarify the risk factors of widespread peritonitis and to improve the treatment and diagnostic algorithms for the management of such patients. Aim - to establish the features of the occurrence of widespread peritonitis and the influence of MTHFR gene polymorphisms on the risk of its occurrence. Materials and methods. The study included 100 patients who underwent surgical interventions for acute abdominal diseases complicated by peritonitis: acute appendicitis (48%), acute cholecystitis (32%), perforated ulcer of the stomach or duodenum (8%), tumor perforation (3%), injuries of the abdominal cavity (3%), pinched hernia (2%) and intestinal obstruction (4%). Genotypes of MTHFR gene polymorphisms rs1801131 and rs1801133 were determined by real-time polymerase chain reaction. Mathematical processing of the research results was carried out using the Statistica 10 program. Results. The risk of disseminated peritonitis was increased with perforated gastric or duodenal ulcer, tumor perforation, abdominal trauma, herniated hernia, or intestinal obstruction compared with acute appendicitis and cholecystitis. The risk of disseminated peritonitis was lower in II blood group carriers compared and was associated with temperature at hospitalization and pulse rate. Conclusions. The factors determining the risk of disseminated peritonitis in the multivariate regression model were the diagnosis, heart rate, and the rs1801131 genotype of the MTHFR gene. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.