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Pylephlebitis is defined as septic thrombophlebitis of the portal vein or one of its tributaries. Pylephlebitis is an uncommon and often fatal complication of intra-abdominal infections, such as diverticulitis and appendicitis. The most common bacteria isolated from patients with pylephlebitis are Escherichia coli and Bacteroides fragilis. The overall mortality rate is 32%. We describe a case of septic thrombophlebitis of the main portal vein and inferior mesenteric vein successfully treated with broad-spectrum antibiotics and anticoagulants. The early diagnosis and treatment with the timely administration of antibiotics is most important for pylephlebitis.