Abstract Objective To compare the mortality rates of patients with claudication and de novo femoropopliteal lesions treated with and without paclitaxel coated devices (PCD). Background A recent meta-analysis, mostly including patients with claudication and de novo femoropopliteal lesions but also with recurrent stenoses and critical limb ischemia, has shown a significant excess mortality in patients treated with PCD. Methods Comparison of two historical cohorts of patients presenting with claudication and de novo femoropopliteal lesions treated with and without PCD between 2008 and 2018. Results After review of 5219 arteriograms in patients presenting with peripheral artery disease, 700 consecutive patients were included consisting in 72.6% of male (n = 508). Mean age was 68.1 ± 8.5 years. 45.7% of the patients (n = 320) had a treatment including a PCD. Mean femoropopliteal lesion length was 123 ± 91 mm including 44.6% of occlusions. Patients of the control group were censored at crossover to paclitaxel when applicable. Mortality rates at 1, 2 and 5 years were 4.6%, 7.5%, 19.4% and 1.6%, 6.2%, 16.6% in the non-PCD and PCD groups respectively. The relative risks of death when using PCD were 0.35 (p = 0.03), 0.83 (p = NS) and 0.86 (p = NS) at 1, 2 and 5 years respectively. Conclusion There was no excess mortality in patients with claudication and de novo femoropopliteal lesions treated with paclitaxel coated devices at 1, 2 and 5 years of follow-up in this cohort. The current study suggests that additional prospective randomized studies properly powered to study mortality are necessary.