Both the recently updated consensus guidelines published by the American College of Chest Physicians, and the International Union of Angiology recommend thromboprophylaxis with either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) in medical patients at risk of VTE. However, no guidance is given regarding the appropriate dosing regimens that should be used for thromboprophylaxis in this patient group. LMWH (enoxaparin and dalteparin) and UFH have been shown to be effective for thromboprophylaxis in at-risk hospitalized medical patients. Although LMWH once daily (o.d.) has been shown to be as effective as UFH three times daily (t.i.d.) for thromboprophylaxis in at-risk medical patients, there are no data to show that UFH twice daily (b.i.d) is as effective as either LMWH o.d. or UFH t.i.d. On the basis of currently available evidence, the LMWHs enoxaparin and dalteparin are more attractive alternatives to UFH for the prevention of VTE in hospitalized medical patients because of their convenient once-daily administration and better safety profile, demonstrated in terms of reduced bleeding, HIT, and other adverse events.