To analyze the effect and safety of root canal therapy with warm vertical compaction technique in patients with combined periodontal-endodontic lesions. Methods A total of 80 patients with combined periodontal-endodontic lesions admitted to the Department of Stomatology, Changping District Hospital of Beijing from January to December 2022 were randomly divided into observation group and control group, with 40 patients in each group. The control group was treated with root canaltherapyfillingwithcold lateral gutta-percha compaction, and the observation group was treated with root canaltherapy fillingwithwarm vertical compaction technique. The clinical efficacy, filling effect, periodontal index and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 95.00%, which was higher than 77.50% in the control group (P <0.05). The excellent and good rate of filling in the observation group was 97.50%, which was higher than 80.00% in the control group (P <0.05). The periodontal index level of the two groups after treatment was lower than that before treatment, and that of the observation group was lower than that of the control group (P <0.05). The incidence of adverse reactions in the observation group was 5.00%, which was lower than 22.50% in the control group (P <0.05). Conclusion Compared with cold lateral gutta-percha compaction, root canal therapy fillingwith warm vertical compaction technique is more effective in patients with combined periodontal-endodontic lesions, which can further improve the filling effect and the periodontal health level of patients. Meanwhile, the risk of adverse reactions after treatment is low and the safety is high.