The objective of this study is to evaluate the efficacy and safety of purse-string suture compared with manual compressing for hemostasis in children with atrial septal defect (ASD) after large-caliber venous delivery sheath removal. We conducted a retrospective study of 271 children with ASD were treated with transcatheter closure of the large-calibe venous delivery sheath (≥ 8 Fr) at our center from January 2018 to January 2023. The control group (n = 127) underwent manual compression for femoral venous hemostasis after removal sheaths. The purse string suture (PSS) group (n = 144) underwent PSS technique. Contrast clinical data on hemostatic time, limb braking time, bed rest time, hospital stay and complications (rebleeding, hematoma formation, local blood ooze, skin ecchymosis and skin damage) between two groups of patients. Compared with the control group, the average hemostatic time (4.63 ± 1.95 vs. 19.69 ± 5.64) min, limb bending time (6.83 ± 2.25 vs. 13.45 ± 2.87) h and bed rest time (8.69 ± 1.43 vs. 22.93 ± 2.24) h were significantly shorter in the PSS group, compared to the control group (P < 0.001). The differences regarding hospital stay and complications between the two groups were statistically insignificant (P༞0.05). Conclusions: The PSS is a straightforward, effective, and secure procedure for attaining rapid hemostasis after removal of large-calibe venous delivery sheath (≥ 8 Fr) for transcatheter closure of ASD in children. The PSS enables pediatric patients to access earlier mobilization and physical activity, a shorter bed rest duration and relief of discomfort when compared to manual compression.