MynxGrip is a non-suture, balloon catheter- and extravascular sealant-based vascular closure device designed to help hemostasis after an arterial puncture. This study evaluated the efficacy and safety of MynxGrip versus manual compression for femoral artery access closure in patients undergoing diagnostic or interventional procedures.The PANDA multicenter, parallel-group, open-label, randomized controlled trial enrolled patients undergoing a diagnostic or interventional procedure through femoral artery access between April 2019 and September 2020 at six centers in China. The participants were randomized 2:1 to the MynxGrip group and the manual compression group. Time to hemostasis and incidence of severe complications were the primary efficacy and safety endpoints, respectively.A total of 304 consecutive participants were included. The baseline characteristics were similarly distributed in the MynxGrip (n = 203) versus manual compression (n = 101) groups. Compared with the manual compression group, the median time to hemostasis and time to ambulation were significantly shorter (3.0 (interquartile range: 2.0, 4.0) vs 18.0 (11.0, 22.0) min, and 479.0 (275.0, 932.0) vs 1410.3 (1121.0, 1476.0) min, respectively; both p = 0.0001) in the MynxGrip group, with similar procedural success rate, and without severe complications in either group. The incidence of device-related adverse events was 11.8% in the MynxGrip group, most possibly or definitely unrelated.Compared with manual compression, the MynxGrip vascular closure device significantly shortens the times to hemostasis and ambulation without severe complications after diagnostic or interventional procedures through the femoral artery access.