Background and Clinical Significance: Pylephlebitis is a suppurative thrombophlebitis of porto-mesenteric veins. It is a rare complication of intraabdominal infection or inflammation. Case Presentation: A 46-year-old female patient presented to the Emergency Department (ED) with a three-day history of subfebrile body temperature (37.5 °C) and dull pain in the right lower abdominal quadrant propagating to the left lower quadrant, with frequent bowel movements and liquid stool consistency. Inflammatory markers were elevated. Following transabdominal ultrasound, possible diagnoses were inflammatory changes of the appendix or sigmoid colon. She was given oral antibiotics and discharged home with a surgical follow-up the next morning. The next day, due to the worsening of the symptoms, surgery was performed with no additional imaging studies. Intraoperative findings were diverticulitis of the sigmoid colon with perforation and peritoneal inflammation, and primary anastomosis with a diverting ileosotomy was performed. The patient was discharged from the hospital after seven days with completed antibiotic treatment. Twelve days later, the patient presented to the ED with a two-day fever (38 °C), elevated inflammatory markers and imaging findings consistent with pylephlebitis: complete left portal vein thrombosis, partial thrombosis of the segmental branch of the right portal vein and thrombosis of the inferior mesenteric vein. The administration of anticoagulants and antibiotics started and after nine days she was discharged home. Conclusions: Timely treatment is a necessity in patients with diverticulitis to prevent complications. Furthermore, clinicians and radiologists should be familiar with vascular complications of diverticulitis because their detection and the following treatment can prevent more extensive disease.