Aims: Given the complexity of antithrombotic therapy guidelines especially in patients with combined antithrombotic therapy, there is a risk of inappropriate prescribing and medication errors. In order to prevent this, a multidisciplinary antithrombotic stewardship (ASP) is implemented in our hospital. The primary aim of this study is to determine the efficacy of this ASP by assessing the number of patients on combined antithrombotic therapy for whom one or more interventions are needed. Methods: A prospective cohort study in a large teaching hospital is conducted. Hospitalized patients who received combined antithrombotic therapy in which an oral anticoagulant was combined with one (double therapy) or two (triple therapy) platelet aggregation inhibitors were included. The ASP proactively evaluated the appropriateness of this combined antithrombotic therapy. If needed, ASP improved the concerned therapy. Each improvement measurement by ASP was counted as one intervention. Results: A total of 460 patients were included over a period of 12 months. 251 (54.6%) patients required at least one intervention from the ASP. The most common intervention was to define and document a maximum duration of the combined antithrombotic therapy (65.5%) instead of lifetime use of the combination, to discontinue antithrombotic therapy (19.4%) as the proper indication was lacking and to adjust the dosage (8.1%). Conclusion: As intervention was needed in more than half of the patients on combined antithrombotic therapy, it seems essential to implement an ASP that dedicated evaluates antithrombotic therapy to improve and ensure optimal use and medication safety.