Background: This study aimed to assess the safety and efficacy of EXOSEAL vascular closure device (EVCD) insertion by comparing its performance with manual compression (MC) in achieving hemostasis at the brachial artery puncture site. Methods: A retrospective study of brachial artery access by using either MC or EVCD for achieving hemostasis from March 2016 to October 2017 was conducted. Patients with Stanford type B aortic dissection (TBAD) undergoing percutaneous transbrachial procedures were included. Time to hemostasis (TTH) was the primary efficacy end point. Seven-day incidence of major access siteerelated complications was the primary safety end point. TTH and major and minor complications associated with treatment of these 2 groups were also evaluated. Results: A total of 157 patients with TBAD undergoing percutaneous transbrachial procedures entered the analysis. Of these, 107 patients underwent EVCD insertion and 50 patients underwent MC. The baseline characteristics of the 2 groups were similar. TTH was significantly shorter for EVCD over MC (P < 0.05). The TTH 10 min in the MC group was 100.0% (n ¼ 50), but in the EVCD group, it was 2 min, 87.9% (n ¼ 107); 2e5 min, 7.5% (n ¼ 107); and 10 min, 4.7% (n ¼ 107). The EVCD group had several major complications, while the MC group had none. Two patients (1.9%, n ¼ 107) required vascular repair, one patient (0.6%, n ¼ 107) required blood transfusion, and 1 patient (0.6%, n ¼ 107) developed upper limb numbness and weakness after EVCD deployment. Minor complication such as the occurrence of hematoma (5 cm) in the MC group was 4 (8.0%) but was also 4 (3.7%) in the EVCD group, showing statistically significant difference (P ¼ 0.030). The incidence of ecchymosis was Xiaolong Wei, Tonglei Han and Yudong Sun contributed equally to this work.