Portal vein thrombosis (PVT) is a heterogeneous entity often described as either an acute or chronic occlusion of the portal vein or its tributaries. The clinical presentation is highly variable, and it often mimics other more common causes of abdominal pain. In most patients, imaging studies such as doppler ultrasound, computed tomography, or magnetic resonance imaging are adequate for diagnosis. Occasionally imaging studies may be inadequate, and the diagnosis may not be made until complications such as bowel necrosis and perforation have occurred. We present a case of a morbidly obese 45-year-old female who was initially treated for suspected small bowel enteritis and discharged home on several occasions after nonspecific findings on abdominal imaging were seen and interval improvement in symptoms occurred with intravenous fluids and antibiotics. She then presented with worsening symptoms and was found on abdominal imaging to have a large fluid collection in the peritoneal cavity requiring exploratory laparotomy with peritoneal washout and partial small bowel resection due to perforation. She was diagnosed with PVT with mesenteric extension after samples of the resected mesentery were evaluated in the pathology laboratory. Her treatment included a prolonged course of antibiotics, total parenteral nutrition, and anticoagulation.