HIV-associated obstructive portopathy (HIVOP) is an obstruction of the hepatic microvasculature of unknown origin. The purpose of this study was to describe the clinical and paraclinical presentation of the disease and its impact in terms of morbidity. Twenty-nine HIV1-infected patients (average 12 years of infection, nadir of CD4 210/mm, including 7 patients with a history of opportunistic infection) with a biopsy-proven or likely HIVOP have been followed up for an average of 6.1 years. Modes of revelation of the HIVOP were: cytolysis and/or cholestasis (60%), occult (14%) or symptomatic (37%) portal hypertension (esophageal varices 17%, ascites 10%, cytopenia 10%), or fortuitous (8%). Hypoalbuminemia (≤35 g/L) was present in (31%), thrombocytopenia (<150,000 platelets) in 52% and prothrombin rate <70% in 10%. Esophageal varices were detected in 71%. Thrombophilia was present in 23 patients (80%): in head, protein S deficiency (87%). MRI showed in 82% at least 1 morphological abnormality. The average value of the liver stiffness by Fibroscan was 8.3 kPa. During follow-up, there was no radiological improvement, 15 (52%) patients presented with variceal hemorrhage, 10 patients (34%) ascites, 10 (34%) portal vein thrombosis, 7 (24%) an iron deficiency, and 2 (7%) with a protein-losing enteropathy, including 14 patients (48%) with several events. Four patients (14%) were transplanted, 1 (25%) recurred the HIVOP on the graft, and 1 patient is waiting for a transplant. HIVOP is a severe disease associated with high morbidity related to symptomatic portal hypertension, which occurred in 50% and required liver transplantation in 14%.