BACKGROUND: Odontogenic maxillary sinusitis, often triggered by dental issues like periapical periodontitis, significantly contributes to chronic sinusitis, mainly affecting adults around 50 years old, emphasizing the need for a multidisciplinary diagnostic and treatment approach. AIM: To investigate the therapeutic effect and clinical value of root canal therapy combined with nasal endoscopic surgery compared with simple root canal therapy in the treatment of severe odontogenic maxillary sinusitis caused by periapical periodontitis. METHODS: The clinical data, diagnosis, and treatment of 200 patients with severe odontogenic maxillary sinusitis caused by periapical periodontitis from October 2020 to October 2021 were analyzed retrospectively. Among them, 63 patients were treated with simple root canal therapy as the control group, and 137 patients were treated with root canal therapy combined with nasal endoscopic surgery as the observation group. The therapeutic effect, Lund-Kennedy endoscopic score, paranasal sinus Lund-Mackay score, complication rate, recurrence rate, and patient satisfaction were compared between the two groups. RESULTS: First, we compared the effective rates: 23 cases were cured, 22 were improved, and 8 were ineffective in the control group, yielding a total effective rate of 84.90%. Meanwhile, 97 cases were cured, 34 improved, and 6 were ineffective in the observation group, resulting in a total effective rate of 95.62%. The observation group had a higher total effective rate compared with the control group ( CONCLUSION: Root canal therapy combined with nasal endoscopic surgery has a good therapeutic effect on severe odontogenic maxillary sinusitis caused by periapical periodontitis, and it can reduce the injury of maxillary sinus mucosa and bone, and significantly reduce the incidence of complications and recurrence rate. Meanwhile, it has high patient satisfaction and remarkable therapeutic effect, which is suggested to be popularized and applied in clinic.