BACKGROUND: Patients with peripheral arterial disease (PAD) undergoing percutaneous coronary intervention (PCI) are at elevated risk of ischemic and bleeding events. However, the optimal duration of dual antiplatelet therapy (DAPT) after PCI in patients with PAD is unknown. METHODS: A systematic literature search was performed through June 2017 using PubMed, EMBASE and Cochrane databases with the following key terms: “dual antiplatelet therapy”, “P2Y12 inhibitor”, “myocardial infarction” (MI), PCI and PAD. The analysis was restricted to randomized trials published in English in patients with PAD receiving extended DAPT (≥12-month) after MI or PCI. The Cochrane Risk of Bias Tool was used to assess bias risk. Overall analysis was performed using Review Manager 5.3 with a random-effects model by using the MantelHaenszel method. RESULTS: Two randomized controlled trials involving 895 patients were included in this review. Compared to the placebo group, the occurrence of Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) in patients receiving extended DAPT was lower but not statistically significant (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.37–1.57; p = 0.46). The results were associated with substantial heterogeneity (I2 = 71%, p = 0.07). Extended DAPT was not significantly associated with increased GUSTO moderate/severe bleeding events (OR 1.63, 95% CI 0.84–3.18; p = 0.15; I2 = 0%, p = 0.59). DISCUSSION: Among patients with PAD, extended DAPT after PCI results in a non-significant difference in ischemic and bleeding events compared to placebo, respectively. The review was limited by the small number of published trials. One of the two trials compared the extended DAPT versus short DAPT (≤6-month), which may cause overestimation of the benefits of extended DAPT in MACCE in our results. The routine use of extended DAPT in this cohort should be carefully evaluated. OTHER: Authors have no conflicts of interest. No external funding or registration.