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Background: Owing to the complicated anatomical nature of maxillary molars, untreated root canals may directly affect the outcome of root canal therapy. Therefore, cone beam computed tomography (CBCT) scan is an important tool in the evaluation of root canal systems, particularly for the detection of the second mesiobuccal (MB2) canal in maxillary molars., Aims and Objectives: The current study was undertaken to detect and evaluate filled/unfilled MB2 canals in endodontically treated, asymptomatic maxillary molars, and its correlation with periapical pathology by utilizing cone beam computed tomography (CBCT)., Material and Method: A retrospective study of 80 CBCTs of patients underwent scanning for various treatment modalities, with asymptomatic endodontically treated permanent maxillary first molars selected. Data collection occurred between January and June 2023. CBCT machine used was KODAK 9000 (Rochester, NY: Carestream Health) (Complementary Metal Oxide Semiconductor {CMOS} sensor, continuous mode and 12-28 sec scan time, 90-500 μm voxel size, and 5x3.5 cm field of view {FOV}). The axial images at mid-root level were used to assess the presence of the MB2 canal., Result: The study included 39 (48.8%) right maxillary first molars and 41 (51.3%) left maxillary first molars. Overall, in 62 (77.5%) maxillary first molars, MB2 was missed by the practicing dentist, and in 13 (16.3%) maxillary first molars MB2 canal was not present. Of all the maxillary first molars with MB2 canal (n=67), 53 (79.1%) canals had a periapical infection, five (7.5%) showed widening of periodontal ligament space whereas nine (13.4%) had no abnormality., Conclusion: MB2 canals were present in the majority of cases and most of the unfilled MB2 canals showed evidence of periapical radiolucencies and showed a direct impact on the prognosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Bhargava et al.)