We report a case of an HIV seropositive female patient treated with a protease inhibitor-containing regimen who developed recurrent severe life-threathening episodes of haematemesis over time, caused by ruptured oesophageal varices as a consequence of a portal vein thrombosis. Coagulation tests revealed a protein S deficiency, an elevated homocysteinemia and a constitutional elevated plasma factor VIII coagulant activity. These coagulopathies and the HIV infection are independent risk factors for developing venous thromboembolic events. The protease inhibitor treatment may have played a role in increasing the thromboembolic risk. The recurrent bleedings only stopped after invasive surgery. The invasive splenorenal shunt operation was in this case a life-saving procedure.