Recent literature reports an increased incidence of venous thrombosis following thalidomide use in the treatment of diseases with disease-related thrombotic risks such as malignancy, as well as concomitant use with chemotherapy and/or systemic corticosteroids. We report a case of deep vein thrombosis (DVT) and pulmonary embolism (PE) following thalidomide use in a patient with erythema nodosum leprosum (ENL) reaction who was concurrently treated with prednisolone, as well as a review of relevant literature.