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Aim: To determine the minimum dentin thickness in the mesial and distal walls of the mesiobuccal (MB) and mesiolingual (ML) canals of the mandibular first molars using cone-beam computed tomography (CBCT)., Materials and Methods: CBCT examinations of 624 mandibular first molars from an Indian subpopulation were analyzed. The mesial and distal minimum dentin thickness was evaluated in 1 mm intervals apical to the furcation area. Independent t -test was used to analyze the data ( α  = 0.05). Using Cohen's kappa coefficient, the interexaminer and intraexaminer reliability was evaluated., Results: The mesial dentin thickness was significantly higher than the distal dentin thickness for MB and ML canals ( P =0.01). The average dentin thickness in the distal and mesial plane of the MB canal was 1.15 ± 0.15 mm and 1.52 ± 0.19 mm at the 1 mm level and 0.83 ± 0.13 and 1.08 ± 0.18 at the 5 mm level, respectively. For the ML canal, the average dentin thickness in the distal plane and the mesial plane was 1.24 ± 0.18 mm and 1.44 ± 0.21 at the 1 mm level and 0.91 ± 0.16 and 1.01 ± 0.17 at the 5 mm level, respectively. Statistical analysis between the MB and ML canals showed significant differences in the dentin thickness at 4 and 5 mm levels in both the distal and the mesial planes ( P =0.01). In more than 85% of the cases, the minimum dentin thickness was seen at the 5 mm level in both the distal and mesial planes in MB and ML canals., Conclusion: The distal planes of the mesiolingual and mesiobuccal canals were thinner in most cases, making the distal surface more prone to iatrogenic perforations. Considerably, at 4 and 5 mm from the furcation, the distal wall was significantly thinner than the mesial walls. Understanding the anatomy of the danger zone in the mesial roots of the mandibular first molars may serve to minimize the risk of endodontic mishaps such as strip perforations., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Sahil Choudhari et al.)