Objective To compare the clinical efficacy of drug-eluting stents （DES） with that of drug-coated balloons （DCB） in patients with GLASS stage 3 femoropopliteal atherosclerotic disease. Methods A retrospective analysis was conducted on the clinical data of 104 patients with GLASS stage 3 femoropopliteal atherosclerotic disease who underwent endovascular intervention at the Guangdong Provincial Hospital of Chinese Medicine from December 2020 to December 2023. Among these patients， 52 were treated with Eluvia DES （DES group）， and another 52 were treated with paclitaxel-coated DCB （DCB group）. The primary patency rate and the rate of freedom from clinically driven target lesion revascularization （CD-TLR） at 6， 12， and 24 months were assessed using Kaplan-Meier survival curves. The occurrence of adverse events， such as death and amputation， was also monitored. Results All 104 patients successfully completed the procedure. Kaplan-Meier estimates demonstrated that the primary patency rates at 6， 12， and 24 months after the procedure were 94.1% vs. 94.1%， 84.3% vs. 74.5%， and 76.3% vs. 54.9% for the DES and DCB groups， respectively. Log-rank tests indicated a statistically significant difference in the primary patency rates between the two groups postoperatively （P = 0.030）. The rates of freedom from CD-TLR at 6 months were the same for the DES and DCB groups （98.0% vs. 98.0%）. The rates of freedom from CD-TLR at 12 and 24 months were higher in the DES group than in the DCB group （92.2% vs. 84.3%， 86.1% vs. 66.7%）. Log-rank tests showed a statistically significant difference in the distribution of survival curves for freedom from CD-TLR between the two groups （P = 0.023）. No statistically significant difference was detected in the ankle-brachial index （ABI） between the two groups before the procedure and at 6 months after the procedure. At 12 and 24 months after the procedure， the ABI in the DES group was significantly higher than that in the DCB group （P = 0.033， 0.003）. At 24 months after the procedure， the proportion of patients with an improvement in Rutherford classification of ≥ 2 grades compared to pre-procedure was 72.0% （36/52） in the DES group， significantly higher than the 50.0% （25/50） in the DCB group， and this difference was statistically significant （P = 0.024）. Conclusion In patients with GLASS stage 3 femoropopliteal atherosclerotic disease， DES demonstrate superior mid-term clinical efficacy compared to DCB treatment.