Background <p>Pylephlebitis (or thrombophlebitis) of the portal vein system is defined as infective suppurative thrombosis affecting the portal vein and is a rare pathology associated with high rates of mortality and morbidity due to intra-abdominal infection. This case illustrates the diagnostic challenges, complex clinical course, and successful multimodal management of suppurative pylephlebitis with multiple liver abscesses following laparoscopic appendectomy.</p> Report <p>A 56-year-old White Turkish male patient presented to the emergency room with severe right lower- and middle-quadrant abdominal pain. The patient was septic and had a recent history of laparoscopic surgery for perforated appendectomy. During follow-up, portal vein thrombosis, portal vein thrombophlebitis, and multiple liver abscesses were detected. The patient responded to meropenem and daptomycin antibiotic therapy, with significant clinical and laboratory improvement, and rivaroxaban was used as anticoagulant therapy. Key learning points include the importance of early imaging in culture-negative sepsis following abdominal surgery, the rationale for antibiotic escalation to daptomycin in the setting of prior antibiotic exposure, and the feasibility of rivaroxaban as long-term anticoagulation in non-cirrhotic portal vein thrombosis.</p> Discussion <p>Pylephlebitis is typically observed after diverticulitis and perforated appendicitis of intra-abdominal origin. Thus, bacteremia should be evaluated, repeated blood cultures should be obtained, and a differential diagnosis of thrombosis should be considered. This case illustrates the successful use of rivaroxaban in a patient with multi-organ involvement, highlighting the diagnostic utility of liver biopsy and the importance of a comprehensive differential diagnostic approach in the management of suppurative pylephlebitis.</p>