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Outcomes assessment of retreatment and endodontic microsurgery (EMS) are traditionally based on clinical findings and radiographs. The purpose of this study was to assess the volumetric change of periapical radiolucencies (PARLs) by cone-beam computed tomographic (CBCT)-based analysis in retreatment and EMS cases.For 68 retreatment and 57 EMS cases, preoperative and recall clinical data, periapical (PA) radiographs, and CBCT imaging were retrospectively obtained. Specialized software was used by 2 board-certified endodontists for volumetric analysis of PARLs. For EMS and retreatment, clinical outcomes were determined by combining clinical data with CBCT-generated volumetric analysis (PA radiographs not used). Additionally, comparisons of percent volume reduction for EMS and retreatment were performed. Examiner interpretations of outcomes assessment using PA radiography and CBCT imaging were compared.In teeth with or without a preoperative PARL, EMS resulted in a statistically significant difference in complete healing (49/57 [86.0%]) versus retreatment (28/68 [41.2%], P < .0001). EMS resulted in a statistically significant difference in combined complete healing and reductive healing (54/57 [94.7%]) versus retreatment (56/68 [82.4%], P < .05). Of 46 recalls in which CBCT imaging detected a PARL, PA radiography detected 30 (a 35% false-negative rate). Of the 79 recall studies in which CBCT imaging did not detect a PARL, PA radiography did detect PARL in 13 (a 16.5% false-positive rate).In this CBCT and clinical data-based outcomes assessment, EMS resulted in a greater mean volumetric reduction and a higher healing rate compared with retreatment. Postoperative CBCT imaging is more sensitive and specific than PA radiography in assessing PARL and has demonstrable usefulness in outcomes assessment.