Budd-Chiari syndrome (BCS), characterized by hepatic venous outflow obstruction caused by a hypercoagulable state is usually related to myeloproliferative disorders. Resistance to activation of protein C caused by factor V Leiden mutation (FVLM), presenting as BCS syndrome was first reported in 1995 (Lancet:345:525) and since then is considered the commonest cause of BCS. This report describes 6 patients who were confirmed to have BCS due to FVLM. Five patients were female, age ranged from 16 to 45 years, 5 were of Arab descent, 2 had recurrent abortions and 1 had prior history of deep vein thrombosis. 5 patients were heterozygous for the mutation, 3 had myelo- proliferative disorder and 1 of these had coexistent lupus anticoagulant. Serum bilirubin ranged between 1.0 to 4.5 mg/dl, serum albumin ranged from 3.3 to 4.0gm/dl, prothrombin INR between 1.0 to 1.8, ALT 25 to 62 U/l and AST 25 to 78 U/l. All patients had biopsy confirmation of sinusoidal dilatation and congestion. Two patients received surgical shunts, 1 patient was managed with diuretics alone and 4 patients received anticoagulants in addition. One patient died, 3 were awaiting liver transplantation and 2 were being observed. The authors conclude that FVLM should be evaluated in any case suspected of BCS because the prevalence of this mutation in the general population is high.