Thalidomide is the treatment of choice for severe or recurrent erythema nodosum leprosum. Its use has been associated with deep vein thrombosis in patients with blood disorders, however, particularly when used in combination with corticosteroids or chemotherapy. We describe a case of deep vein thrombosis in a 43-year-old man with lepromatous leprosy who was being treated with thalidomide and prednisone for a type 2 leprosy reaction (erythema nodosum leprosum); the patient also had transiently positive antiphospholipid antibody results. We stress the importance of considering deep vein thrombosis, a potentially fatal complication, in dermatology patients treated with thalidomide.