More than 200 million people worldwide suffer from peripheral arterial occlusive disease (PAOD). As PAOD is a significant risk factor for the occurrence of acute vascular events and, as a result the life expectancy of those affected is also significantly reduced, they are considered high-risk patients. Antithrombotic treatment is one of the most important pharmaceutical cornerstones in the prophylaxis of these events but the effect of acetylsalicylic acid (ASA)-based antithrombocytic monotherapy is limited. There are now indications for the first time that a combination of ASA-based monotherapy with low-dose anticoagulation (rivaroxaban 2 × 2.5 mg) can achieve a significant additional benefit for patients with symptomatic PAOD requiring and not requiring interventions. These new findings have currently been discussed in guidelines and summarized in new recommendations. These results have a significant influence on the peri-interventional and postinterventional antithrombotic treatment of PAOD patients.