Venous thromboembolism is a significant cause of illness and death worldwide. Large bodies of evidence support the heightened risk status of hospitalized medical patients, and that prophylactic measures significantly reduce the risk of thrombosis, yet these patients often fail to receive adequate prophylactic therapy. This failure may be accounted for by a lack of awareness of the relevant indications, poorly designed implementation systems, and clinical concerns over the side effects of anticoagulant medications. This article briefly summarizes our understanding of the clinical factors relevant to the evaluation of venous thromboembolism risk in hospitalized medical patients. We describe our approach to the use of thromboprophylaxis, through which we aim to minimize the disease burden of this under-recognized and preventable pathology.