Objective To analyze the clinical effect and safety of endoscopic highly selective vidian neurotomy on the treatment of moderate to severe persistent allergic rhinitis (PAR).Methods Sixty patients suffering from nasal septal deviation combined with moderate to severe PAR admitted to Huazhong University of Science and Technology Union Shenzhen Hospital from Jan 2018 to Sept 2019 were selected. All the patients were randomly divided into control group (n=26) and treatment group (n=34). The patients in the control group received endoscopic nasal septoplasty and those in the treatment group received endoscopic nasal septoplasty combined with highly selective vidian neurotomy including posterior nasal neurotomy and pharyngeal branch of vidian neurotomy. Total rhinitis medication scores (TRMS), visual analogue scale (VAS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores as well as incidences of local and systemic adverse reactions between the two groups were compared at the timepoints before treatment, 1 month, 3 months, and 6 months after treatment.Results Forty-six cases were followed up for 6 months postoperatively and had complete general data, including 26 in the treatment group and 20 in the control group. Before treatment, the differences of TRMS, VAS and RQLQ scores between the two groups were statistically insignificant (all P>0.05).One month, 3 and 6 months after treatment, the differences of VAS and RQLQ scores between the two groups were statistically significant (all P<0.05), and VAS and RQLQ scores of the treatment group were lower than those of the control. Three and 6 months after treatment, TRMS scores of the treatment group were lower than those of the control group (all P<0.05), while the difference of TRMS score in one month after treatment was statistically insignificant (P>0.05). The differences of pre- and postoperative TRMS in the control group were statistically insignificant (P>0.05), while the TRMS scores in 3 months and 6 months after treatment were lower than those before treatment in the treatment group (P<0.05). The difference of complication rate between the two groups was statistically insignificant (P>0.05).Conclusion The endoscopic highly selective vidian neurotomy is safe and effective for the treatment of moderate to severe PAR.