Suture-mediated closure device and Figure-of-Eight suture are commonly used to achieve hemostasis after use of large bore venous access. Although both methods of closure are commonly used in clinical practice, a head-to-head comparison in a controlled setting has not been performed. Patients presenting to a single center for elective left atrial appendage occlusion or transcatheter edge-to-edge mitral valve repair were randomized to large bore venous closure using the Perclose ProGlide suture-based closure or a Figure-of-Eight suture closure. The patients were followed for 1 month after the procedure. Primary outcome, a composite of access site large ecchymosis, hematoma, infection, pain, need for unscheduled venous ultrasound and need for transfusion, was compared between the 2 arms. A total of 40 patients were randomized in a 1:1 fashion to the 2 venous closure strategies. Baseline characteristics were similar between the 2 groups. Perclose ProGlide arm required use of more devices for hemostasis (1.5 +/- 0.5 vs 1 +/- 0 respectively, p <0.0001), and there was a significant difference in the cost of closure device ($367.00 +/- 122.00 vs $1.00 +/- 0 respectively, p <0.001). At 1 month post-procedure, the primary outcome occurred in 4 patients (20%) in the Perclose arm and 7 (35%) patients in the Figure-of Eight arm, a difference that was not statistically significant (p = 0.48). Time to hemostasis between Figure-of-Eight and Perclose arms did not reach statistical significance (2.5 +/- 2.1 vs 3.7 +/- 2.3, p = 0.09). In conclusion, both Perclose ProGlide suture-based device and Figure-of-Eight closure are equally feasible and safe for patients who underwent large bore venous access. Figure-of-Eight-based closure is more cost effective. (c) 2023 Published by Elsevier Inc. (Am J Cardiol 2023;209:181-183)