Background Research shows impaired endothelial function in patients with vascular diseases and improved endothelial function following revascularization and medical treatment. There is, however, a dearth of data on the effects of different endovascular therapeutic strategies on endothelial function. We sought to compare the effects of two endovascular strategies of drug-coated balloons versus stenting on endothelial function. Methods The reactive hyperemia index, the ankle-brachial index, and the toe-brachial index were measured in patients undergoing endovascular revascularization preprocedurally and on the 90th postprocedural day. After adjusting for baseline line characteristics, reactive hyperemia index were compared between the two groups at baseline and at 90 days. Results Between January 2018 and March 2019, 86 patients were prospectively included in a non-randomized manner. Drug-coated ballooning alone was carried out on 46 patients, and bailout stenting after plain balloon angioplasty was performed on the remaining 40 patients The post-revascularization reactive hyperemia index exhibited a significant rise in both groups (1.58 ± 0.21 vs. 1.43 ± 0.20; P = 0.0001). There was no difference in the postprocedural reactive hyperemia index between the two treatment groups. Additionally, the follow-up reactive hyperemia index showed no significant change compared with the postprocedural reactive hyperemia index (1.58 ± 0.23 vs. 1.57 ± 0.22). The results of subgroup analysis between a group of clinically high-risk patients and a group of patients with complex lesions were similar to the aforementioned results. Conclusions The reactive hyperemia index was significantly improved by endovascular therapy in our study population. However, no difference was observed between drug-coated ballooning and bare-metal stenting, which highlights the effects of vessel patency on endothelial function.