Aim To investigate the clinical efficacy and safety of excimer laser atherectomy (ELA) in the treatment of infrapopliteal arteriosclerosis occlusion, in order to provide more options for intracavitary treatment for patients with infrapopliteal arteriosclerosis occlusion. Methods The clinical data of 50 patients (50 limbs) with infrapopliteal arteriosclerosis occlusion treated in the Department of Vascular Surgery of People's Hospital of Xinjiang Uygur Autonomous Region from December 2019 to December 2021 were collected retrospectively, they were divided into ELA group (n＝25) and plain old balloon angioplasty (POBA) group (n＝25) according to different treatment methods, the clinical characteristics, perioperative complications, primary patency rate, postoperative ankle brachial index (ABI) improvement, visual analogue scale (VSA) and limb salvage rate during follow-up of target vessels of the two groups were compared. Results The success rate of operation in the two groups was 100%, and there were no serious complications during the perioperative period. ABI and VAS scores in the two groups were significantly improved after treatment compared to before treatment, and the ABI in the ELA group was higher than that in the POBA group 3 days and 6 months after operation, with a statistically significant difference (P＜0.05); at 6 months after operation, the VAS score in the ELA group was lower than that in the POBA group, with a statistically significant difference (P＜0.05); during the follow-up period, the first-stage primary patency rate and limb (toe) salvage rate in the ELA group were higher than those in the POBA group (P＜0.05). Conclusion ELA is safe and feasible for the treatment of infrapopliteal arteriosclerosis occlusion, which provides more options for intracavitary treatment of inferior genicular artery lesions.