Aim To discuss the safety and curative efficiency of excimer laser ablation (ELA) combined with drug-coated balloon(DCB) angioplasty treating in-stent restenosis(IRS) of femoral-popliteal artery. Methods This study retrospectively analyzed all 36 clinical data of patients whose femoral-popliteal artery has IRS and treated by excimer laser ablation (ELA) combined with plain old balloon angioplasty(POBA) and DCB angioplasty between March 2017 to Feburary 2018. 36 patients were treated as the observation group, and 57 patients whose treatment is POBA combined with DCB angioplasty were treated as control group. Observe the success rate of surgery, complication rate, minimum lumen diameter (MLD) immediately after surgery, ankle brachial index(ABI) in the third day after surgery etc. Postoperatively follow up ABI in the first, third, sixth, twelfth month after surgery, target lesion revascularization(TLR) rate in twelve months, ISR, amputation rate, MLD, late lumen loss(LLL) etc. Results There was no significant difference between the two groups in terms of gender, age, TASCII grade, and other comorbidities (P>0.05). It analyzed the ABI at 1,3, 6 and 12 months after operation, and the TLR, ISR, amputation rate, MLD and LLL at 12 months after operation.The P values were all less than 0.05, and the observation group was superior to the control group. Conclusion ELA combined with POBA and DCB is safe and effective in the treatment of femoral-popliteal artery ISR, with short and moderate-term effect better than POBA combined with DCB.