Abstract: The aim of the current cone beam computed tomography (CBCT) study was to evaluate the proximity of mandibular first and second molar roots to the inferior alveolar canal (IAC) and mandibular cortex in an Egyptian subpopulation. Scans of 120 patients (480 molars, 960 roots) were obtained from the College of Dentistry database at the Suez Canal University, Egypt. Buccal and lingual bone plates and root thickness were measured at the specified resected root end 3 mm from the radiographic apex, and so was the proximity of the root apices to the IAC. Measurements of the right and left mandibular first and second molars were recorded for each root. Three examiners performed the measurements separately. ANOVA was used to compare the different roots. Bonferroni’s post-hoc test was used for pair-wise comparisons when ANOVA was significant. The significance level was set at p ≤ 0.05. The findings displayed a closer proximity of the mandibular second molar apices to the IAC, as compared to the mandibular first molars. The mesial roots were at a shorter distance than the distal ones. Moreover, the mandibular second molars revealed the thickest total bone width including the root. So, it is beneficial for endodontists to be aware of the relation of the mandibular first and second molars to the surrounding cortical bone plates and the IAC before starting either nonsurgical or surgical endodontic treatment.