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Endovascular treatment of a significant stenosis in an infrainguinal autologous bypass prevents bypass occlusion and improves bypass patency. Drug-eluting balloons (DEBs) have been proven to possess antirestenotic features in the treatment of femoropopliteal stenoses and occlusions. This study evaluated the effects of DEB angioplasty vs uncoated balloon (UCB) angioplasty to rescue infrainguinal autologous bypass grafts at risk (BAR).The study included all consecutive patients treated endovascularly for BAR from December 1, 2012, to July 31, 2015. As of April 1, 2014, the primary treatment of BAR was changed from UCBs to DEBs. Patients treated with DEBs were prospectively recorded in a database and retrospectively analyzed. Patients treated with UCBs were retrospectively collected from a historical cohort with a similar inclusion period length as the DEB cohort. The follow-up scheme did not differ between the two groups. The primary end point was the combined end point of freedom from recurrent stenosis or bypass occlusion. Secondary end points were primary assisted patency, secondary patency, technical success, major amputation, and mortality.Twenty-one patients were treated in the DEB group and 18 were treated in the UCB group. The two groups were evenly distributed in demographics, bypass, treatment, and lesion characteristics. No statistically significant differences were found in the combined end point of freedom from recurrent stenosis and the occlusion rate after 1 year between the UCB group (77.8%) and the DEB group (80.0%; P = .76). After 1 year, the primary assisted patency rate was 88.2% in the UCB group vs 95.2% in the DEB group (P = .47), and the secondary patency rate was 94.1% in the UCB group vs 95.2% in the DEB group (P = .91). During follow-up, restenosis developed in four patients (22.2%) in the UCB group and in four patients (19.0%) in the DEB group (P = .80). One bypass (5.6%) in the UCB group and one bypass (4.8%) in the DEB group occluded during follow-up (P = .884).DEBs and UCBs perform equally in the treatment of significant stenosis in infrainguinal autologous bypasses with regard to freedom from restenosis or bypass occlusion, primary assisted patency, and secondary patency at 1 year. We suggest using a less expensive UCB in the treatment of BAR.