Introduction: Portal system ischemia may present insidiously which may aggravates the prognosis. Case presentation: A 26-year old man presented with watery diarrhea and generalized abdominal pain for 3 months. On physical examination, moderate splenomegaly was noticeable. Stool exam and culture was negative except for blood in stool. Colonoscopy was in favor of inflammatory bowel disease although the patient symptoms have worsened despite treatment. Abdominopelvic computed tomography (CT) showed thromboses in portal and superior mesenteric veins and as the ill patient evolved signs of peritonitis, he underwent laparotomy during which, total colectomy was performed due to significant bowel necrosis. The cause of venous thrombosis of the portal system revealed to be Factor V Leiden and the presence of antiphospholipid syndrome. Conclusion: High mortality rates of portal and mesenteric thromboses despite therapy urge the need for early clinical suspicion, careful assessment of the differential diagnoses and timely treatment for fewer adverse events. Although the therapeutic plan is challenging, anticoagulation, angiography and surgical resection increase survival.