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Background/Objectives: Locating the mandibular foramen (MF) through imaging is clinically important for inferior alveolar nerve (IAN) anesthesia and mandibular ramus osteotomies. Although cone-beam computed tomography (CBCT) is superior in imaging the mandible, an orthopantomogram (OPG) is preferred for its ease of use and availability. Therefore, the present study aimed to evaluate the accuracy of digital OPG in localizing the MF, in a subset of the Middle Eastern population. Methods: Radiographic images (OPG and CBCT) of selected patients (adults, dentulous and no mandibular abnormalities) were used to locate the MF through digital measurements (mm) of the anteroposterior distance from the anterior border of the ramus (MF-AP) and the superoinferior position from the mandibular occlusal plane (MF-SI). Measurements were statistically compared between OPG and CBCT for accuracy. Differences in measurements between OPG and CBCT were compared against the anatomic location (right/left), age and biological sex, assuming a p-value < 0.05 as significant. Results: A total of 204 radiographic records (males: 100/females: 104/mean age: 34.65 ± 11.55 years) were evaluated. The measurements for the MF were MF-AP-OPG (right: 13.53 ± 2.44/left: 13.19 ± 2.25), MF-AP-CBCT (right: 13.61 ± 2.39/left: 13.36 ± 2.19), MF-SI-OPG (right: 5.25 ± 1.71/left: 5.41 ± 1.65) and MF-SI-CBCT (right: 5.59 ± 1.66/left: 5.52 ± 1.61). Measurements between OPG and CBCT were not significantly different, except for MF-SI (right) (p = 0.042). While the overall difference between OPG and CBCT (MF-AP/MF-SI) measurements showed a significant association (p < 0.01) with the anatomic location (right/left), a significant association (p < 0.05) with biological sex was observed only for MF-AP. Conclusions: Based on this study’s outcomes, digital OPG is an accurate modality to locate the MF based on anteroposterior (MF-AP) and superoinferior (MF-SI) measurements. This would be clinically beneficial for dental and oral surgeons to achieve the optimum IAN block anesthesia based on preoperative panoramic radiographs. Similarly, it would assist maxillofacial surgeons in planning mandibular orthognathic surgeries and ramus osteotomies without complications.