Objective:To explore the clinical efficacy of percutaneous balloon compression (PBC) in the treatment of trigeminal neuralgia (TN) based on the double difference (DID) model.Methods:A retrospective case - control study method was adopted to analyze the general data of 130 patients with trigeminal neuralgia (TN) who were treated in the Department of Neurosurgery of Hebei General Hospital from January 2022 to October 2023. Among them, 49 were males and 81 were females. The age was (53.28±11.67) years, ranging from 25 to 80 years old. According to different treatment methods, the patients were divided into an experimental group ( n=63) and a control group ( n=67). Patients in the experimental group were given percutaneous balloon compression (PBC) treatment, while those in the control group were treated with conservative drug therapy. Propensity score matching method was used for 1∶1 matching. After matching, there were 52 cases in each group. The general data of the two groups were compared. The visual analogue scale (VAS), 36-item short form health survey (SF-36) score, Hamilton depression rating scale (HAMD) score, Hamilton anxiety rating scale (HAMA) score, 5-hydroxytryptamine, neuropeptide P, inflammatory factor interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) before and after treatment, as well as the clinical efficacy of the two groups of patients were comparatively analyzed. Meanwhile, the incidence of postoperative complications in the two groups was compared. The generalized estimating equation (GEE) model was used to analyze the influencing factors of clinical efficacy, and the difference-in-differences (DID) model was used to evaluate the efficacy before and after treatment. Measurement data conforming to the normal distribution were expressed as mean±standard deviation ( ± s), and the t-test was used for comparison between groups; the chi- square test was used for comparison between count data. Results:After treatment, the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, and TNF-α level in the experimental group were (2.98±0.83) points, (75.56±1.18) points, (7.2±0.83) points, (7.15±0.85) points, (76.34±5.47) ng/mL, (50.95±11.01) pg/mL, (29.45±7.08) ng/L, and (21.18±3.55) ng/L respectively. In the control group, there were (3.63±0.95) points, (73.23±1.13) points, (7.98±0.80) points, (8.04±0.84) points, (186.31±11.61) ng/mL, (86.52±13.32) pg/mL, (34.47±6.58) ng/L, and (26.36±5.80) ng/L, respectively. The differences between the two groups were statistically significant ( P<0.05).The cure rate and the total incidence of postoperative complications in the experimental group were 55.77% and 13.46% respectively, while in the control group, they were 40.38% and 30.77% respectively. The differences between the two groups were statistically significant ( P<0.05).The results of the GEE model analysis showed that age, course of disease, VAS, SF-36 score, HAMA score, HAMD score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, TNF-α level, treatment method, and the long - diameter ratio of FO significantly affected the clinical efficacy of patients ( P<0.05).The results of the DID model showed that the experimental group was superior to the control group in improving the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, and TNF-α level( P<0.05). Conclusion:PBC can significantly improve the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine, neuropeptide P, IL-1, TNF-α, and incidence of complications in patients with TN. It can also improve the psychological status and quality of life of patients.