Objectives <p>The primary aim of this randomised clinical trial was to compare the one year clinical and radiographic outcome of mature permanent central incisors with periapical radiolucencies in adolescents after root canal retreatment using two regenerative endodontic procedures (REPs) with revitalization using induced blood clot formation (BC) or platelet-rich fibrin (PRF) evaluated with cone-beam computed tomography (CBCT). The secondary aim was to assess the responses of the teeth to thermal and electric pulp tests.</p> Materials and methods <p>Fifty-four root filled maxillary central incisors with post-treatment endodontic disease and periapical radiolucencies in 48 adolescents were allocated into two groups (<i>n</i> = 27) using permuted block randomisation. The teeth in one group were root canal retreated with induced BC formation and teeth in the other with PRF. At baseline and at one year, teeth were evaluated clinically and radiographically using periapical radiographs and CBCT scans. Changes in the maximum diameter and volume of the periapical lesions were assessed and pulp sensibility was assessed at one year using thermal and electrical tests. Differences in lesion diameter and volume between the two groups were tested using the Mann–Whitney U test. A linear regression model explored the relationship between independent variables and lesion size. The significant level was set at 5%.</p> Results <p>Reduction in periapical lesion size in the BC and PRF techniques occurred in 85% and 100% of teeth, respectively, with no significant difference. In the BC group, the mean lesion volume diminished from 0.33 ± 0.18 cm³ to 0.13 ± 0.20 cm³, while the mean volume of lesions in the PRF group decreased from 0.27 ± 0.16 cm³ to 0.04 ± 0.06 cm³ with no significant difference between the groups (<i>P</i> &gt; 0.05). Significantly more teeth responded positively to thermal (<i>P</i> = 0.028) and electric (<i>P</i> = 0.032) tests in the PRF group compared to the BC group.</p> Conclusions <p>REPs using BC or PRF techniques when retreating root canal-treated mature permanent central incisors in adolescents with apical radiolucencies had comparable clinical and radiographic outcomes one year following treatment associated with significantly more positive responses to thermal and electric pulp tests in the PRF group.</p> Clinical relevance <p>Retreatment of mature permanent teeth with apical periodontitis using regenerative endodontic procedures (REPs) is a new and promising approach. REPs with platelet-rich fibrin (PRF) and revascularization techniques provided high and comparable clinical and radiographic success rates.</p>