Laparoscopic cholecystectomy is now the gold standard for the treatment of symptomatic cholelithiasis. Portal venous thrombosis after laparoscopic cholecystectomy is rare. We report a case of thrombosis of the portal venous system after laparoscopic cholecystectomy in a patient with a latent prothrombin gene mutation. An abdominal computed tomography and magnetic resonance angiogram of the abdomen revealed portal, superior mesenteric, and splenic vein thrombosis. Testing for coagulation disorders showed a heterozygous form of factor II (prothrombin) G20210A mutation. Because of its rarity, information regarding this complication is limited.