Pylephlebitis, or suppurative thrombophlebitis of the portal mesenteric venous system occurring in the setting of abdominal inflammatory processes, is a rare but deadly disease commonly associated with diverticulitis. We review our institutional experience in the management of patients with this condition. A retrospective review of medical records from 2002 to 2012 was performed. Patients with a portal mesenteric vein thrombosis (PMVT) within 30 days of an intra-abdominal inflammatory process were identified and evaluated. Ninety-five patients were included. The mean patient age at presentation was 57 years (range, 24-88). The most common associated processes were pancreatitis (31 %), followed by diverticulitis (19 %). Bacteremia was noted in 34 (44 %) patients. The most common organism cultured was Streptococcus viridans. Antibiotic and anticoagulation therapy was given in 86 (91 %) and 78 (82 %) patients, respectively. Overall, we report an 11 % mortality rate. Albeit rare, pylephlebitis most commonly was manifested in the setting of pancreatitis. Treatment should be individualized to culture results and extent of thrombosis. If diagnosed early and managed appropriately, a favorable outcome is possible.