Objectives: Extraction of mandibular third molars carries the risk of injuring the inferior alveolar nerve. The risk can be minimized by modifying the surgical approach or technique but this requires a thorough assessment of the relationship between the third molar and the mandibular canal. This study aims to analyze available data that compares the accuracy of panoramic radiographs and Cone Beam CT images in assessment of the relationship between the mandibular third molars and the inferior alveolar nerve canal. Methods: A systematic search of the English literature using several databases was conducted. Articles between the years 2004 and 2014 were selected on the basis of predetermined inclusion criteria. They were then reviewed against a checklist for diagnostic tests and analyzed for pertinent data. Results: Only two studies met the inclusion criteria and were included in the meta-analysis. Overall sensitivity for CBCT was 0.94 and overall specificity was 0.51, both of which were higher than panoramic radiographs but not statistically significantly different than panoramic radiographs. Conclusions: The limited available evidence suggests that panoramic radiographs are as accurate as Cone Beam CT is assessing the relation of the mandibular third molar to the mandibular canal. Although Cone Beam CT offers vital information in the buccolingual dimension that is valuable in the pre-extraction treatment-planning phase.