To compare the diagnostic accuracy of periapical radiography (PR) and cone-beam computed tomography (CBCT) for detecting pathoses of endodontic origin using the gold standard of direct surgical visualization. Seventy-four patients (112 teeth) underwent radiographic examination by periapical radiography and CBCT. The presence of periapical lesions, root perforations and their locations, root fractures, different types of external root resorptive defects, apicomarginal bone defects, through and through bone defects, buccal bone status and proximity of root apices and lesions to vital anatomical structures were assessed. These same parameters were assessed intraoperatively by direct surgical visualization which served as the gold standard reference for the radiographic assessments. Sensitivity, specificity, positive predictive values, negative predictive values were determined for comparison of diagnostic accuracy between two modalities. There were no significant differences between the two imaging modalities for root resorptive defects and root fractures. However, CBCT accurately detected periapical lesions, root perforations, apicomarginal bone defects and through and through bone defects. The overall accuracy of CBCT varied from 91% to 96% in detecting dehiscence and fenestration of buccal cortical plates. Overall, CBCT had a higher diagnostic accuracy in complex endodontic pathoses compared to PR. Nevertheless, CBCT failed to diagnose apicomarginal bone defects in 33% teeth. In evaluating the status of buccal cortical plate from CBCT images, observers could detect absence of bone better than its presence. Thus, limited FOV CBCT should be considered for selective cases where periapical radiography has diagnostic ambiguity.