Objective To analyze the effect of one-appointment root canal therapy in the clinical treatment of patients with chronic pulpitis. Methods A total of 80 patients with chronic pulpitis admitted to our hospital from January 2021 to July 2022 were selected as the research objects and divided into experimental group and reference group by random number table method, with 40 cases in each group. The reference group was treated with multiple root canal therapy, and the experimental group was treated with one-time root canal therapy. The quality of life, clinical efficacy were compared between the two groups, and clinical indicators (postoperative pain time, medication time). Results After treatment, the scores of physical function, role function and mental state in the experimental group were higher than those in the reference group (P <0.05). The total effective rate of treatment in the experimental group was 97.50%, which was higher than 80.00% in the reference group (P <0.05). There was no significant difference in postoperative pain time and medication time between the two groups (P >0.05). Conclusion The use of oneappointment root canal therapy in the clinical treatment of patients with chronic pulpitis has a good effect, which can improve the quality of life, reduce pulp pain, and improve prognosis. It is worthy of clinical application.