A recent meta-analysis of 4663 patients reported higher 2- and 5-year mortality in patients with femoral-popliteal artery occlusive disease treated with paclitaxel-coated balloons and stents compared with plain balloon angioplasty and bare metal stenting. Our aim was to compare mortality after similar treatments using a multicenter vascular registry. Patients (n = 6992) without prior peripheral vascular intervention undergoing endovascular treatment of superficial femoral-popliteal artery occlusive disease in the Vascular Quality Initiative (VQI) were studied from September 2016 to September 2017. All-cause mortality was compared between patients treated with nondrug-coated devices (n = 3905) versus paclitaxel-coated balloons and/or eluting stents (paclitaxel group; n = 3087). Mortality rates with hazard ratios (HR) and 95% confidence intervals (CI) were compared between unadjusted and propensity matched cohorts and illustrated by Kaplan-Meier analysis. Subgroup analysis was performed for intermittent claudication and critical limb ischemia (CLI). Mortality was higher in the nondrug group (13.4%) compared with the paclitaxel group (10.8%) in the unmatched cohorts (HR, 0.80; 95% CI, 0.69-0.93; P < .01). After 1:1 propensity matching the paclitaxel (n = 2440) and nondrug-coated device (n = 2440) groups were similar except for differences at the extremes of age and symptom status (CLI 54% vs 59% respectively; P < .01). Mortality was similar for the nondrug group (13.2%) and paclitaxel group (11.5%) after propensity matching (HR, 0.87; 95% CI, 0.73-1.04; P = .12) at a mean follow-up of 509 days (17 months; range, 0-813 days [0-27 months]). Subgroup analysis of patients with claudication showed no mortality difference in the matched cohorts; nondrug coated device (5.1%; n = 41/804) and paclitaxel (3.8%; n = 32/842; HR, 0.74; 95% CI, 0.46-1.17; P = .20). Subgroup analysis of patients with CLI showed no mortality difference in the matched cohorts; nondrug-coated device (18.9%; n = 191/1012) and paclitaxel (18.5%; n = 200/1081) groups (HR, 0.99; 95% CI, 0.81-1.20; P = .90). By Kaplan-Meier analysis mortality was similar in the paclitaxel versus nondrug device group (Fig). At a mean follow-up of 17 months, mortality is similar for patients with claudication and CLI after treatment of femoral-popliteal occlusive disease with paclitaxel coated and nondrug coated devices. Additional VQI analysis is planned for 2019 to assess for mortality differences at later time points. This work highlights the potential use of the VQI for surveillance of the safety of new peripheral arterial devices.