BACKGROUND: Percutaneous microballoon compression (PMC) is an important clinical technique for the treatment of trigeminal neuralgia (TN). Some studies have shown that patients may be infected with herpes simplex virus type 1 (HSV-1) after surgery. However, the prevalence and associated risk factors are unclear yet. This study aimed to explore the potential risk factors of facial herpes simplex (FHS) in patients with TN treated by PMC retrospectively. METHODS: A retrospective study included 181 patients with TN undergoing PMC treatment between September 2019 and August 2020 in Sichuan Cancer Hospital and Institute. Depending on whether the patient was infected with HSV-1 after PMC operation or not, the patients were divided into two groups, FHS group and non-FHS group, respectively. Demographic, clinical, laboratory, and surgical data of the patients were collected. Univariable and multivariable logistic regression analysis were used to explore the risk factors of infecting with HSV-1 in patients with TN after PMC. RESULTS: Among 181 patients with TN treated by PMC surgery without FHS. 49 patients were diagnosed with FHS after operation, and the diagnosis was confirmed by PCR detection of HSV-1. All patients had no FHS before operation, the occurrence of FHS was 27.07% (49/181) in patients underwent PMC. Variables with p<0.05 in univariable analysis included gender (male/female), age, duration of disease and CD8+ T cells count. The results of multivariable logistic regression analysis showed the independent risk factors of FHS after PMC were gender (male/female) (p<0.01, OR 0.061, 95% CI 0.009~0.428), age (p<0.001, OR 1.169, 95% CI 1.065~1.283), duration of disease (p<0.001, OR 1.361, 95% CI 1.206~1.535) and CD8+T cells count (p<0.01, OR 0.993, 95% CI 0.989~0.998). CONCLUSIONS: In our study, we found that elderly patients and duration of disease were the risk factors of occurring FHS in TN patients after PMC surgery. CD8+T cells count and male gender were the protective factors for not developing FHS.