Pylephlebitis, also called septic thrombophlebitis of the portal vein, is a life-threatening complication of intra-abdominal infection. Although rare, it remains a less recognized entity with a high rate of mortality. We present a 66-year-old man with acute infected choledocholithiasis complicated with Bacteroides fragilis bacteremia. The contrast-enhanced computed tomography scan of the abdomen showed nearly total thrombotic occlusion of the left portal vein. The comprehensive studies for hypercoagulation disorders all yielded negative results. After endoscopic extraction of bile duct stones and broad-spectrum antibiotic therapy, the patient recuperated with complete recanalization of the occluded portal vein. To our knowledge, pylephlebitis associated with acute infected choledocholithiasis has never been reported. This report details the clinical features, radiographic findings, pathogenesis, and treatment of this distinctly unusual manifestation. Early identification of pylephlebitis and underlying intra-abdominal infection can be achieved by exquisite imaging studies with raised awareness in the clinical setting. Eradication of infectious foci and judicious administration of antimicrobials are essential to reduce the catastrophic morbidity and mortality of pylephlebitis.