Abstract Patients hospitalized for acute medical and surgical illnesses are at risk of developing venous thromboembolism (VTE) during hospitalization and after discharge. Extended pharmacological prophylaxis beyond the hospital stay is recommended for patients undergoing surgeries at high risk for VTE and for selected groups of hospitalized medical patients. This practice involves several challenges, from identification of at-risk populations eligible for extended prophylaxis to choice of the most appropriate anticoagulant and definition of the ideal duration of use. This review will present the main VTE risk assessment models for hospitalized medical and surgical patients, the current recommendations for use of extended prophylaxis, and its limitations and benefits.