© 2020 American Heart Association, Inc. Background: To compare mortality after treatment of superficial femoral-popliteal artery disease with paclitaxel and nonpaclitaxel devices using a multicenter vascular registry. Methods: Patients (N=8376) undergoing endovascular treatment of superficial femoral-popliteal artery disease in the Society for Vascular Surgery Vascular Quality Initiative were studied from October 2016 to December 2017. One-year mortality was compared between 3 groups; plain balloon angioplasty (N=2104) versus paclitaxel-coated balloon angioplasty (N=3543), bare-metal stenting (N= 2045) versus paclitaxel-eluting stents (N=684), and combined paclitaxel versus nonpaclitaxel devices. Mortality rates with hazard ratios (HR) and 95% CI were compared in unadjusted and propensity-matched cohorts and illustrated by Kaplan-Meier analysis with subgroup analysis for intermittent claudication, chronic limb-threatening ischemia, and secondary interventions. Results: In propensity-matched analyses, mortality was similar after plain balloon angioplasty (12.6%) and paclitaxel-coated balloon angioplasty (9.6%; HR=0.84 [95% CI, 0.66-1.06], P=0.14). In propensity-matched groups, mortality was similar after bare-metal stenting (9.8%) and paclitaxel-eluting stenting (8.8%; HR=0.93 [95% CI, 0.62-1.41], P=0.75). In the combined, matched analysis mortality was significantly lower in the paclitaxel device group (8.5%) compared with the nonpaclitaxel device group (11.5%; HR=0.82 [95% CI, 0.68-0.98], P=0.03). Secondary interventions were similar after nonpaclitaxel (N=1113/4149, 26.8%) and paclitaxel device use (N=1113/4227, 26.3%). For intermittent claudication, mortality was lower after paclitaxel device use (1.6%) compared with nonpaclitaxel devices (4.4%; adjusted HR=0.59 [95% CI, 0.39-0.89], P=0.01). For chronic limb-threatening ischemia, the mortality difference was not significant; paclitaxel (12.8%) versus nonpaclitaxel devices (15.5%; adjusted HR=0.85 [95% CI, 0.72-1.00], P=0.05). Conclusions: At 1 year, mortality was similar if not lower after treatment of femoral-popliteal occlusive disease with paclitaxel versus nonpaclitaxel devices. This work highlights the potential use of the Society for Vascular Surgery Vascular Quality Initiative for surveillance of the safety of new peripheral arterial devices.