Since the mid '90s, the concept of evidence-based medicine has grown exponentially, contributing to the advancement of personalized medicine, which considers the "female gender" as an extremely important area of customization, but orphan of targeted research. Strong evidence do exists demonstrating gender differences in bleeding risk associated with antithrombotic treatment, mostly related to lower values of body mass, organ size and renal function in women than men. Across clinical studies, the search for the specific risk of bleeding in the female vs male gender has gained attention only recently; therefore, data from different studies and relatively limited meta-analyses should be assessed carefully. As for antiplatelet therapy for primary prevention, the risk of major bleeding events, such as cerebral hemorrhage, is lower for women than for men. Conversely, in acute situations in which antithrombotic drugs are given in association, the risk of bleeding is greater for women, in particular for combination therapies with heparin or low molecular weight heparin or thrombolytic agents. Numerous studies in the literature evaluated the incidence of minor and major bleeding during oral anticoagulant therapy in relation to gender, but the results are not entirely consistent and appear to vary over the years. In summary, there are some aspects of guidance in the complex spectrum of the bleeding risk related to antithrombotic treatment, with indications of a lower bleeding risk in women than men related to long-term preventive single antithrombotic drug treatments. In addition, hormonal effects and use of outprescribed drugs may also play a significant role in modulating hemostasis.