The question 'What is the best prophylaxis for venous thromboembolism in the critically ill?' is clinically relevant. The answer is formulated based upon the best available evidence with a focus on pharmacological prophylaxis and symptomatic venous thromboembolism. Four randomized controlled clinical trials with a grade I level of evidence are discussed in detail. Unfractionated heparin is the best studied pharmacological prophylaxis in addition to enoxaparin and nadroparin. The endpoints in these studies all concerned deep venous thrombosis detected by imaging techniques and unrelated to symptoms. The clinical relevance of these endpoints is debatable. No firm conclusions can be drawn on the efficacy and safety of unfractionated heparin, enoxaparin and nadroparin in the prevention of symptomatic venous thromboembolism in the critically ill. As a consequence, no true recommendations can be given for the prevention of venous thromboembolism in these patients. Copyright © 2009, Nederlandse Vereniging voor Intensive Care. All Rights Reserved.