Recent or continued immobility is a significant risk factor for venous thromboembolism (VTE) in acutely ill medical patients. Patients may benefit from thromboprophylaxis; however, its optimal duration remains unclear. The Extended Clinical Prophylaxis in Acutely Ill Medical Patients (EXCLAIM) study was the first trial to systematically investigate how the degree of immobilization relates to the risk of developing VTE. EXCLAIM offers insights into the duration of VTE risk associated with reduced mobility and helps identify which patients would benefit most from extended-duration thromboprophylaxis. Further recent studies suggest that extended-duration thromboprophylaxis may be in order in certain high-risk patients to protect the patients from the risk of VTE events occurring, particularly in the posthospitalization period. Baseline d-dimer data and level of mobility could be included in risk assessment. Physicians are recommended to consider the use of extended-duration thromboprophylaxis based on individual risk assessment management (RAM) and balance of benefit and harm.