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Introduction: Knowledge regarding the root canal morphology is a key for successful root canal therapy. Maxillary molars comprise a complex root canal system. Thus, this study aimed to evaluate the root morphology and root canal configurations of maxillary molars using cone-beam computed tomography (CBCT) radiographic analysis in a Saudi subpopulation. Materials and Methods: The CBCT images of 624 maxillary molar teeth from 208 patient records (age: 28.74 ± 9.56 years) were analyzed using i-Dixel three-dimensional imaging software. Sagittal, axial, and coronal serial sections were used to examine the number of roots, root canal configuration, the number of canals, and differences between the right and left sides. Frequencies and percentages were used to represent the results. Differences between both sides were determined by the Chi-square test, and the significance level was set at P < 0.05 for all statistical tests. Results: In the first molars, 85.8% of teeth had four canals, 14.2% had three canals, 48.2% mesiobuccal (MB) roots had Vertucci Type IV configuration, and both distobuccal and palatal roots had Vertucci Type I roots. In the second molars, three and four canals were present in 33.6% and 66.4% of the teeth, respectively. All the second molars had Vertucci Type I distobuccal and palatal roots, whereas the MB roots were present in 32.9% of the teeth. No significant difference was found between both sides (P > 0.05) for all parameters. Conclusions: Wide variations were found among the same population, and the presence of four canals in maxillary molars was commonly observed. Clinicians should be aware of such differences and use available diagnostic tools, such as CBCT and dental operative microscopy.