Pharmacological prevention of venous thromboembolism (VTE) is primarily focussed on thrombin inhibitors, mainly, cumarins (warfarin), low molecular weight heparins (LMWH) and, more recently, new, direct acting oral anticoagulants (NOAC). However, there may also be a role for aspirin. Several large, though mostly nonrandomized trials in patients undergoing joint surgery (hip, knee) do suggest that aspirin as part of a multimodal approach is not inferior to warfarin or LMWH in primary prevention of VET. Similar considerations appear to apply for secondary longterm prevention of recurrent VTE after the end of guide-line directed anticoagulation. New experimental data in mouse models of VTE demonstrate a potent, partially thromboxane-mediated, antithrombotic action of low-dose aspirin which is related to its antiplatelet effect. In addition, low-dose aspirin and salicylate were also shown to inhibit the local expression of inflammatory genes, including cytokines and COX-2, possible amplifiers of the thrombotic process. These data provide new mechanism-based support for possible benefical actions of aspirin in prevention of VTE which are not shared with warfarin-type anticoagulants or Factor Xa-inhibitor-type NOACs. A final assessment of the role of aspirin in prevention of VTE is not possible yet. Direct head-to-head comparisons with NOAC are indispensable and are in progress (EPCAT-II; EINSTEINCHOICE). The patient´s individual risk profile needs also to be considered. This includes comorbidities, as well as the possible requirement of long term antiplatelet treatment wirth aspirin for prevention of arterial thromboembolism (myocardial infarction).