The risk of cardiovascular events increases considerably after an acute coronary syndrome (ACS), particularly in the first few months. Dual antiplatelet therapy represents the mainstay of secondary prevention during this period, but is associated with a not-negligible risk of bleeding which, among other factors, is influenced by the platelet count. Thrombocytopenic patients may experience an ACS, and several patients with ACSs develop thrombocytopenia during hospitalization: the management of antithrombotic therapy in this setting represents a challenge. Here, we review the available evidence on the use of antithrombotic therapy in patients with low platelet counts after an ACS.