INTRODUCTION: Periapical images are routinely made in endodontics to support diagnosis and treatment decisions, but conventional imaging may not readily demonstrate inflammatory changes. This study aims to quantify disagreement in the radiologic interpretation of apical periodontitis/rarefying osteitis between 2 expert examiners and to determine if differences exist based on anatomic location. METHODS: We used 1717 pretreatment periapical images made before orthograde endodontic treatment as part of the Predicting Outcomes of Root Canal Treatment (PREDICT) study conducted within the National Dental Practice-Based Research Network. Periapical changes were assessed independently by 2 board-certified specialists, an oral and maxillofacial radiologist and an endodontist, blinded to other clinical information. If the examiners disagreed about whether a diagnosis of apical periodontitis/rarefying osteitis was justified, an adjudication was made by a third examiner. RESULTS: The overall prevalence of this radiologic diagnosis in the periapical images was 55%, and interexaminer agreement measured with the Cohen kappa statistic was calculated to be 0.56 (95% confidence interval, 0.52-0.60). Diagnostic disagreements between the 2 examiners occurred for 377 teeth (22%), with disagreements more frequent for jaw location (P = .038) and tooth type (P = .021). Differences between root number (P = .058) and jaw location and tooth groups (P = .069) were found not to be statistically significant. CONCLUSIONS: The variability of diagnostic disagreements across anatomic location and tooth type may reflect the inability of periapical images to reveal bone changes masked by the complexity and density of overlying anatomic structures, a limitation that could potentially be overcome with the use of 3-dimensional imaging.