Background and Objectives: There is limited information regarding comparison of long-term dynamics of periapical bone destruction estimated by digital periapical radiography (DPR) and by cone-beam computed tomography (CBCT). This study aimed to compare the radiographically assessed periapical changes of endodontically treated teeth over 2 years of follow-up and to analyse disagreements in periapical lesion size estimates around the same roots using DPR and CBCT. Materials and Methods: A total of 176 endodontically treated teeth, of 128 patients with apical periodontitis, were assessed by DPR and CBCT, at baseline and after 2 years. All periapical radiolucencies were categorised by severity (S0, S1, S2, S3) concerning their size. Descriptive statistics were used to report distribution of the radiolucencies at baseline and at follow-up, and their size transitions over 2 years. Site-specific comparison of the radiolucencies identified by two methods was performed using Z test and Pearson's chi-square test. Results: majority of the detected radiolucencies were scored as S0: 65% and 68% at baseline; 89% and 83% at follow-up, by DPR and CBCT, respectively. Site-specific score comparison showed that disagreements comprised 18% and 20% of the total number of radiolucencies detected by DPR and CBCT, respectively. There were more disagreements between DPR and CBCT within categories S1 and S2 + S3 compared to S0: at baseline, they comprised 17-33% and after two years 62-95% of all detected radiolucencies within the category. 65% of non-matching score transitions over two years occurred between S0 and S1. The CBCT-based evaluation resulted in negative treatment outcomes for 10 more root canals than the DPR-based result. Conclusions: Most remarkable disagreement between DPR and CBCT recordings was observed within the radiolucency categories S2 and S3. However, the diagnostic accuracy of both radiographic methods was questionable as it resulted in a high proportion of non-matching S0-S1 lesion transitions over 2 years.