Abstract Body (Do not enter title and authors here): Peripheral artery disease (PAD) increases the risk of cardiovascular events, such as stroke and myocardial infarction. Antiplatelet therapy, particularly aspirin, has been essential in the management of PAD, although its effectiveness may be limited in high-risk patients. Recently, ticagrelor, a P2Y12 receptor inhibitor, has been shown to be an effective alternative or adjunctive treatment to aspirin. However, the optimal therapeutic strategy for PAD remains unclear, especially when comparing dual therapy with ticagrelor plus aspirin with monotherapy with either antiplatelet agent alone. While dual therapy has been shown to be effective in other cardiovascular diseases, its impact on PAD outcomes, particularly safety and efficacy, requires further investigation. A systematic search was performed in PubMed, Scopus, Embase, and Web of Science, following PRISMA guidelines, including studies up to March 19, 2025. We included only randomized controlled trials (RCTs) comparing the use of ticagrelor plus aspirin with monotherapy antiplatelet alone in patients with PAD. Our main outcomes were myocardial infarction, mortality, limb ischemia, and hemorrhagic events. Hazard Ratio (HR) with 95% Confidence Intervals (CI) were calculated using a random-effects model. Heterogeneity was assessed with I2 statistics. Three RCTs were included from 280 studies obtained through the search. In 1,702 patients, no statistically significant differences were found in myocardial infarction (HR: 1.18; 95% CI: 0.70-1.96; p=0.54), mortality (HR: 0.73; 95% CI: 0.49-1.08; p=0.12), limb ischemia (HR: 0.64; 95% CI: 0.39-1.05; p=0.08), and hemorrhagic events (HR: 1.27; 95% CI: 0.32-4.99; p=0.74) between dual therapy and monotherapy.This meta-analysis is the first to evaluate the comparative effectiveness of dual treatment with ticagrelor plus aspirin versus monotherapy with either antiplatelet agent alone in patients with PAD. Although the results indicated no statistically significant differences between the two treatment strategies in terms of myocardial infarction, mortality, limb ischemia, or bleeding events, the absence of a clear benefit of dual therapy suggests that monotherapy may be a reasonable approach for the management of PAD in these patients. However, given the limitations of this analysis, including the number of studies, further RCTs are necessary to confirm these findings and provide more definitive guidance on the optimal treatment strategy for PAD.