Lower limb peripheral arterial disease (PAD) affects 20% of population over 65 years. Extracorporeal shockwave therapy (ESWT) has recently emerged as a novel, safe, and effective treatment option. This review aims to assess the mechanism of action by which ESWT improves symptoms in patients with PAD.MEDLINE and EMBASE databases were searched in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Any article investigating the mechanism of action of ESWT in PAD was considered for inclusion.The systematic review of the current literature yielded 8 relevant articles reporting studies on animal models of hind limb ischemia or on patients with PAD. These articles described the effects of ESWT on angiogenesis, arteriogenesis, vasculogenesis, endothelial nitric oxide synthase, lower limb micro/macrocirculation, and atherosclerosis.ESWT increases the expression of angiogenic, arteriogenic, and vasculogenic factors, reduces vessel wall stenosis, and improves limb perfusion. However, most of the evidence is based on animal studies. Future research should focus on elucidating the mechanism of action of ESWT in PAD patients.