Prevention of deep vein thrombosis has become standard of care in surgical and orthopaedic patients and it is gaining in attention in medical patients. However, there are still open questions related to its indication, to type and extent of prophylaxis and how to improve its efficacy and safety. In order to facilitate decision making to provide or to withhold prophylaxis, clinical risk assessment considering exposing and predisposing risk factors has proved to be of value. The exposing risk is characterised by type and extent of surgery or trauma, respectively, whereas the predisposing risk is determined by patient related risk factors. This has also been acknowledged in national and international guidelines. The choice of prophylactic modalities should be based on the combination of exposing and predisposing risk factors. Physical and pharmacological methods are available for primary prevention of VTE. The cornerstones of pharmacological prophylaxis have been subcutaneous injections of low molecular weight heparins or fondaparinux. Recently, also oral direct thrombin- and factor Xa-inhibitors have become available for patients undergoing hip or knee replacement surgery who always are at high risk for VTE complications.