Aim To evaluate the safety and clinical efficacy of high atrial septal pacing (HASP) and compare the difference between HASP and right atrial appendage pacing (RAAP) in atrial electrical activity and atrial structure.Methods A retrospective analysis of 142 patients with sick sinus syndrome(SSS)who underwent dual-chamber pacemaker implantation in the Department of Cardiology of the Second Affiliated Hospital of Harbin Medical University from January 2013 to January 2017 was performed. According to the implantation site of atrial pacing lead, the patients were divided into two groups:HASP group (n＝100) and RAAP group (n＝42). Preoperative and postoperative P-wave duration, P-wave dispersion, left atrial diameter, and atrial lead pacing parameters (pacing threshold, perception, impedance) were recorded, and retrospective analysis and comparative study were conducted. Results There were no significant differences in gender, age, previous disease, history of smoking and drinking among the 142 patients enrolled. The duration of P-wave in RAAP group was (128.03±17.11) ms before operation and (144.82±21.37) ms after operation, the duration of P-wave in HASP group was (125.48±13.20) ms before operation and (102.08±15.23) ms after operation, there was a statistically significant difference in the postoperative P-wave duration between the two groups (P＜0.001). The dispersion of P-wave in RAAP group was (27.33±10.12) ms before operation and (18.64±6.59) ms after operation, the dispersion of P-wave in HASP group was (27.12±8.58) ms before operation and (18.89±4.85) ms after operation. The dispersion of P-wave after operation in both groups was reduced compared with that before operation, but there was no significant difference between the two groups (P＝0.47). It seemed that there were no difference between RAAP and HASP in left atrial diameter (34.07±5.71) mm vs. (32.48±4.19) mm (P＝0.10). The pacing parameters in the HASP group were stable, and no additional complications were observed in this group. During the program-controlled follow-up 1 year after the pacemaker implantation, 16.7% of the patients in the RAAP group had atrial fibrillation (AF), while the percentage was only 4.0% in the HASP group, the difference between the two groups was statistically significant (P＝0.015). After 2 years following, there was 28.6% patients in RAAP group having AF, only 17.0% in HASP group, the two groups had no statistical significance. Conclusion HASP is a safe and feasible pacing method that can significantly shorten the P-wave duration and is expected to reduce the risk of atrial fibrillation in patients.