This study aimed to compare the three index systems designed for cone-beam computed tomography (CBCT) in terms of intra- and inter-observer agreement. 117 root-filled teeth with or without periapical radiolucency from 77 of already existing CBCT images were chosen randomly. Two observers evaluated the periapical status of the selected teeth and graded the scores twice using CBCT periapical index (CBCTPAI), endodontic radiolucency index (ERI) and complex periapical index (COPI) part of the periapical and endodontic status scale (PESS), respectively. The researchers' self-agreement kappa values ranged from substantial to almost perfect. A moderate inter-observer agreement was present for the COPI and ERI, whereas a fair agreement was present for CBCTPAI. The researchers' ICC for the inter-observer reliability of CBCTPAI, ERI and COPI was 0.75, 0.77 and 0.80, respectively. COPI had the highest self-agreement and inter-observer reliability. ERI showed the highest intra-observer variation, whereas CBCTPAI showed the highest inter-observer variation.