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Venous thromboembolism (VTE) is the third most common cause of vascular mortality worldwide and comprises deep-vein thrombosis (DVT) and pulmonary embolism (PE). In this review, we discuss how an understanding of VTE epidemiology and the results of thromboprophylaxis trials have shaped the current approach to VTE prevention. We will discuss modern thromboprophylaxis as it pertains to genetic risk factors, exogenous hormonal therapies, pregnancy, surgery, medical hospitalization, cancer, and what is known thus far about VTE in COVID-19 infection.