Objectives <p>This exploratory randomized clinical trial evaluated the regenerative potential of autologous dental pulp transplantation, with or without concentrated growth factor (CGF), compared with conventional root canal therapy (RCT). The aim was to assess sensibility recovery and periapical healing in necrotic mature teeth with periapical radiolucency.</p> Materials and methods <p>Twenty-one patients were randomly allocated into three groups (<i>n</i> = 7): autologous pulp transplantation, pulp transplantation with CGF, and conventional RCT. Donor pulp tissues were obtained from non-carious third molars. Follow-up examinations were performed at 3, 6, and 12 months. Sensibility was assessed using electrical pulp testing, and periapical healing was evaluated by periapical radiographs and cone-beam computed tomography. Statistical analyses included non-parametric tests (Kruskal–Wallis and Wilcoxon) and categorical comparisons (chi-square/Fisher’s exact) (α = 0.05).</p> Results <p>Positive sensibility response was observed in 71.4% of teeth in the pulp transplantation group and 42.9% in the CGF group, while no sensibility recovery occurred in the RCT group. All groups showed periapical healing, with the greatest lesion reduction in the pulp transplantation group (<i>p</i> &lt; 0.01). No adverse events were reported.</p> Conclusions <p>Autologous dental pulp transplantation appears to be a safe and promising approach for necrotic mature teeth, whereas the addition of CGF did not provide additional clinical benefit in this cohort.</p> Clinical relevance <p>Autologous dental pulp transplantation may represent a viable regenerative alternative to conventional RCT in necrotic mature teeth, with the potential to promote periapical healing and partial sensibility recovery without additional biological adjuncts.</p>