Deep vein thrombosis and pulmonary embolism, the common clinical manifestations of venous thromboembolism (VTE), are among the most preventable complications of hospitalized patients. However, survey data repeatedly show poor rates of compliance with guideline-based preventive strategies. This has led the Centers for Medicare and Medicaid Services to deny reimbursement for hospital readmission for thromboembolic complications in patients undergoing total hip or knee arthroplasty. Multiple strategies and national initiatives have been developed to improve rates of VTE prophylaxis during hospitalization; however, most VTE occurs in the outpatient setting. Epidemiologic data suggest that recent surgery or hospitalization is a strong risk factor for the development of VTE and that this risk may persist for up to 6 months. These observations call into question whether VTE prophylaxis should be administered only during hospitalization or if this preventive strategy should be continued after hospital discharge. Many of the randomized trials showing efficacy of VTE prophylaxis have used longer durations of prophylaxis than are typical for current length of hospital stay, highlighting the issue of how long the duration of prophylaxis should be. Several patient groups have undergone formal testing to evaluate the risks and benefits of extended-duration VTE prophylaxis, but this issue is less clear for other categories of patients. Although there is clear consensus that most hospitalized patients should receive VTE prophylaxis, there is uncertainty about whether to continue VTE prophylaxis in the immediate post-hospital period or for an extended duration. The transition from inpatient to outpatient care is a key event in the coordination of continuity of care, but VTE-specific care transition guidance is limited. In this article, we review the evidence for both standard- and extended-duration VTE prophylaxis and discuss the difficulties in effectively maintaining VTE prophylaxis during the transition from inpatient to outpatient care.