The pharmacological prevention of venous thromboembolism (VTE) has so far been carried out mainly with classic (low-molecular-weight heparins, coumarins) or new direct oral anticoagulants (DOACs). The role of antiplatelet treatment with aspirin is controversial. New data, however, suggest a paradigm shift with the reassessment of aspirin as part of a multimodal antithrombotic approach. The article provides an up-to-date overview of the role of antiplatelet treatment with aspirin in the primary and secondary prevention of VTE. Primary prevention of surgery-related VTE with anticoagulants is effective but apparently not superior to a multimodal approach with aspirin, pneumatic compression, and early mobilization. Against this background, aspirin is now also included in the VTE prevention guidelines in the US (ACCP, AAOS) but not in the UK (NICE) and Germany (AMWF). A final evaluation of aspirin as compared to classic anticoagulants and DOACs in primary prophylaxis requires further randomized controlled, prospective trials. These should also consider the iatrogenic risk of bleeding as well as possible postoperative complications, such as retarded wound healing that might require prolonged hospitalization. After ending guideline-conforming anticoagulant treatment in patients with idiopathic VTE, administration of aspirin reduces the risk of recurrent VTE by about 40% without increasing the risk of severe bleeding (standardized INSPIRE evaluation of ASPIRE and WARFASA data). These data add to the current use of aspirin in the prevention of arterial thrombosis the new option of preventing spontaneous VTE. On the basis of new data from recent studies, an indication can be made for the use of aspirin, combined with other preventive measures, in the prevention of primary and secondary venous thromboses.