Peripheral artery disease (PAD) is associated with increased risk for arterial thromboembolic events, and antithrombotic therapy is fundamental to its treatment. Females with PAD have unique characteristics that impact their disease experience, but data is lacking on the differential effects of antithrombotic regimens in females with PAD. We developed a protocol and conducted two systematic reviews and meta-analyses to 1) assess the impact of female sex on cardiovascular, limb, and bleeding events in antithrombotic trials enrolling PAD patients, and 2) evaluate the representation of female PAD patients in antithrombotic trials, as well as trial generalizability. Females did not confer any benefit from dual antiplatelet therapy, dual pathway inhibition, or therapeutic oral anticoagulation over mono-antiplatelet therapy alone, however trial generalizability was limited by poor female enrolment and insufficient sex-based analyses. A more tailored approach to secondary prevention in females with PAD (beginning with improved study design) may yield better outcomes.