Background: The aim of this randomized clinical trial was to evaluate the effects of photodynamic therapy (PDT) after traditional activated final irrigation protocol (ultrasonically activated irrigation, UAI) on periapical lesion healing after single-visit root canal retreatment.Methods: We included 36 patients with asymptomatic chronic apical periodontitis with periapical lesions larger than 5 mm and teeth sensitive to percussion and palpation, who had previous root canal treatment. All patients who signed informed consent underwent cone-beam computed tomography (CBCT) to determine and calculate the preoperative volume of the periapical lesion. Patients were randomly distributed into two groups according to the final disinfection protocol: Group 1; UAI (NaOCl, EDTA, and NaOCl), Group 2; UAI + PDT. All patients underwent single-visit root canal retreatment using rotary instrumentation and standardized irrigation (3 % NaOCl) by the same endodontist. The root canals were filled with epoxy resin-based sealer and single-cone guttapercha, followed by control radiography. After one year, a new CBCT scan of the teeth was performed to calculate the reduction in the initial periapical lesion as a measure of periapical healing. For the statistical analysis, the chi-square test variants, Fisher's exact test and the Fisher-Freeman-Halton test were used at the level of significance set at 5 %.Results: There were no significant differences between the groups in terms of age, sex, preoperative and postoperative lesion volume (p > 0.05), and reduction of periapical lesion volume (median, 86.98 % for UAI and 79.72 % for UAI+PDT) (p = 0.970). Additional use of PDT after UAI did not contribute to the healing of periapical lesions. Conclusion: The UAI and UAI+PDT protocols had equal effects on healing of periapical lesion.