Intrahepatic noncirrhotic portal hypertension can be idiopathic or associated with known toxic, developmental, vascular, or biliary tract diseases. Most patients are successfully managed medically or with shunting procedures. The goal of this study was to explore the reasons some patients require orthotopic liver transplantation (OLT). The clinical features, gross and microscopic liver explant pathology, and posttransplantation course in 16 patients who underwent OLT for intrahepatic noncirrhotic portal hypertension were studied. There were 11 men and 5 women with a mean age of 47 years. Clinical manifestations included gastrointestinal varices (n = 12), ascites (n = 8), encephalopathy (n = 3), and hepatopulmonary syndrome (n = 3). Cirrhosis was misdiagnosed clinically, radiographically and/or histologically in 13 patients (81%). Grossly, liver explants weighed a mean of 1,100 g, and 12 had a nodular appearance. Histologically, all 16 livers had portal tract vascular abnormalities, 15 had nodular regenerative hyperplasia (NRH), and 9 had incomplete septal cirrhosis. After OLT, mild NRH features were noted in 2 patients, and 1 of these patients developed evidence of portal hypertension. This study demonstrates that a subset of patients with intrahepatic noncirrhotic portal hypertension have severe symptoms requiring OLT. Accurate pre-OLT diagnosis is frequently difficult at advanced stages of the disease; 81% of our patients carried a diagnosis of cirrhosis. Morphologically, the explanted livers showed evidence of vascular abnormalities, NRH, and increased fibrosis, but not cirrhosis. Importantly, however, a diagnosis of cirrhosis is not required in this group of patients to qualify them for OLT, and these patients have good long-term graft function after OLT.