OBJECTIVES: Antithrombotic therapy (ATT) prevents atherothrombotic events (AE) in patients with peripheral arterial disease (PAD). However, the benefit may be compromised by poor medication adherence (MA). Therefore, our primary objective was the proportion of patients with PAD with poor MA in literature following patient-reported, pharmacy-reported or laboratory-reported outcome measurements. Poor MA is a combined outcome of primary non-adherence (inability to initiate a prescription), secondary non-adherence (incorrect daily intake) and non-persistence (discontinuation of daily intake). DESIGN: Systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. DATA SOURCES: PubMed, EMBASE and Cochrane Library were searched from 2000 to June 2023. ELIGIBILITY CRITERIA: Publications with a (sub)cohort of patients with PAD that reported on patients' MA to ATT were included. DATA EXTRACTION AND SYNTHESIS: All articles were reviewed on eligibility and methodological quality by two independent researchers. The data were retrieved and collected in Review Manager Web and the percentages were calculated per subgroup. The risk of bias was assessed by using the Cochrane risk-of-bias tool for randomised controlled trials (RCT) and the methodological index for non-randomised studies score for non-RCTs. RESULTS: We identified 274 potential records of which 10 studies (32 628 patients) were included. Six studies were RCTs and two prospective and two retrospective studies. Most studies scored a moderate risk of bias and had heterogeneous study designs. Poor MA rates ranged between 2% and 45%. Higher rates of poor MA were found in studies with longer follow-ups, pharmacy-reported outcome measurements and registry-based cohorts. CONCLUSION: Heterogeneous study designs create a wide dispersion in the proportions. However, poor MA to ATT was found in approximately one-third of the patients with PAD and seemed to increase with longer therapy duration, which highlights the magnitude of this societal challenge. Enhancing patients' MA to ATT might be a key element in reducing the risk of AE, and therefore, more attention to MA in clinical and research settings is warranted. PROSPERO REGISTRATION NUMBER: CRD42023431803.