Bleeding from portal hypertensive gastropathy (PHG) can pose a therapeutic challenge. Thalidomide, which selectively inhibits tumour necrosis factor-alpha production by enhancing messenger RNA degradation, has been shown to reduce portal venous pressure in cirrhotic and non-cirrhotic portal hypertension. Thalidomide is also a potent inhibitor of angiogenesis. We describe a case of intractable bleeding from PHG secondary to extrahepatic portal vein obstruction due to malignancy, which was managed successfully by thalidomide, thus obviating the need for major surgery. Although the use of thalidomide for treatment of severe intestinal bleeding has been described previously, this is the first case report, to our knowledge, describing its efficacy in bleeding secondary to PHG. We discuss the possible therapeutic mechanisms for thalidomide in PHG.