Purpose: A previously healthy 46-year-old-man presented to the emergency department with melena. He also described fevers, chills, anorexia, and postprandial pain, treated with ibuprofen. Temperature was 102.3F, blood pressure 80/35 mmHg, heart rate 104/min, respiratory rate 20/min. Abdomen was mildly tender in the right upper quadrant. There was no stigmata of chronic liver disease. Rectal exam showed brown stool. Nasogastric lavage was clear. WBC count 12,600/uL (95% neutrophils); Hemoglobin 8.3 g/dL; platelets 147,000/uL. Sodium 127 mEq/L; BUN/Creatinine normal. Total bilirubin 1.8 mg/dL; direct bilirubin 1.1 mg/dL; remaining liver profile normal. Albumin 2.0 g/dL; total protein 4.6 g/dL; cholesterol 90 mg/dL. INR 1.3. Abdominopelvic CT showed “dilated intrahepatic biliary ducts, mainly right lobe…probably cholangitis.” EGD found erosive esophagitis and gastritis. ERCP revealed a normal biliary system without defect or dilation. Repeated review of the CT suggested thrombus in the right portal vein, mimicking dilated biliary ducts, confirmed with abdominal ultrasound. Blood cultures grew Streptococcus intermedius in 4/4 bottles. Given the constellation of acute portal vein thrombosis (PVT), fever, abdominal discomfort, bacteremia/sepsis, the diagnosis of pylephlebitis was made. Pylephlebitis is septic thrombophlebitis of the portal vein and its tributaries. Intra-abdominal infection predisposes microthrombi formation, extension of which results in this rare cause of acute PVT. Diverticulitis has replaced appendicitis as the most common underlying primary infection. The hallmark of pylephlebitis is its remarkably vague presentation. In three well referenced series, 100% had fever, 74-100% abdominal pain, and 23-79% were bacteremic. Other features include leukocytosis and abnormal liver function tests; jaundice is a late finding. Enteric organisms are most frequently isolated, especially the uniquely thrombogenic Bacteroides species. S. intermedius has been reported in 2 other cases. This is the first English language case in which S. intermedius is the sole organism. Antibiotics and eradication of the primary infection are mainstays of therapy; the role of anticoagulation is still debated. Mortality remains significant at 10-50%. In this case, the presenting issue was the result of NSAID induced esophagitis/gastritis, itself resultant from the abdominal symptoms associated with pylephlebitis. Anemia and hypotension were initially attributed to GI bleeding, though in context of other findings, are entirely consistent with sepsis. Heightened awareness of this morbid condition, heralded only by its classically ambiguous presentation, will expedite recognition and treatment.