Objective To evaluate the safety and effectiveness of subcutaneous "Z" suture for hemostasis at the femoral vein puncture point after removing large sheaths. Methods A total of 263 patients who were treated by atrial fibrillation cryoablation or leadless cardiac pacemaker (LCP) implantation in The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from May 2020 to Dec. 2021 were enrolled. A 16-French sheath catheter was used in patients treated with atrial fibrillation cryoablation, and a 27-French sheath catheter was used in patients treated with LCP implantation. According to envelope method, the patients were randomly assigned (1:1) to 2 groups:figure-of-eight suture group (132 cases) or subcutaneous "Z" suture group (131 cases), for hemostasis at the femoral vein puncture point. The suture time, hemostasis effect, complication incidence, and patient comfort of the 2 groups were compared. Results There were no significant differences in the suture time, immediate hemostasis rate, or complication incidence between the 2 groups (all P>0.05). The physiological dimension score (17.8±1.6 vs 12.7±2.2), psychological dimension score (33.1±2.7 vs 26.4±3.5), and overall score (84.2±3.4 vs 73.5±5.6) of the Kolcaba's comfort scale in the subcutaneous "Z" suture group were significantly higher than those in the figure-of-eight suture group (all P<0.05). Conclusion Subcutaneous "Z" suture can achieve safe and effective hemostasis at the femoral vein puncture point after removing large sheaths, and the comfort of patients is higher than those with figure-of-eight suture.