To assess the safety and efficacy of routine use of ultrasound-guided puncture and the use of vascular closure device (VCD) in patients undergoing endovascular therapy (EVT) through femoral access. This was a single-center, non-randomized clinical study that enrolled 513 patients undergoing EVT via femoral artery access in which hemostasis was achieved using VCDs (406-patient EXOSEAL arm and 107-patient PROGLIDE arm). All cases were performed by routine use of ultrasound-guided access. The primary endpoint was the achievement of hemostasis without periprocedural and 30-day incidence of major or minor access site-related complications. The primary endpoint was achieved in 91.6 % of the cases (470/513) with a higher success rate in the EXOSEAL arm (93.6). Major complications were observed in 5 patients (0.9 %) in total cohort and 3 patients (0.7 %) treated with EXOSEAL arm vs. 2 patients (1.8 %) with PROGLIDE arm (p = 0.32). Combined treatment two VCDs with the routine ultrasound guidance access for patients who underwent the EVT procedure showed high efficacy and safety outcomes.