Tooth autotransplantation (TAT) offers a viable biological approach to tooth replacement in children and adolescents. The aim of this study was to evaluate the outcome of the cone-beam computed tomographic (CBCT)–guided TAT compared to the conventional TAT protocol and to assess the 3-dimensional (3D) patterns of healing after CBCT-guided TAT (secondary aim). This study included 100 autotransplanted teeth in 88 patients. Each experimental group consisted of 50 transplants in 44 patients (31 males and 19 females). The mean (SD) age at the time of surgery was 10.7 (1.1) y for the CBCT-guided group. This was 10.6 (1.3) y for the conventional group. The mean (SD) follow-up period was 4.5 (3.1) y (range, 1.1 to 10.4 y). Overall survival rate for the CBCT-guided TAT was 92% with a success rate of 86% compared to an 84% survival rate and a 78% success rate for the conventional group (P > 0.005). The following measurements were extracted from the 3D analysis: root hard tissue volume (RV), root length (RL), apical foramen area (AFA), and mean and maximum dentin wall thickness (DWT). Overall, the mean (SD) percentage of tissue change was as follows: RV gain by 65.8% (34.6%), RL gain by 37.3% (31.5%), AFA reduction by 91.1% (14.9%), mean DWT increase by 107.9% (67.7%), and maximum DWT increase by 26.5% (40.1%). Principal component analysis (PCA) identified the mean DWT, RV, and maximum DWT as the parameters best describing the tissue change after TAT. Cluster analysis applied to the variables chosen by the PCA classified the CBCT group into 4 distinct clusters (C1 = 37.2%, C2 = 17.1%, C3 = 28.6%, C4 = 17.1%), revealing different patterns of tissue healing after TAT. The CBCT-guided approach increased the predictability of the treatment. The 3D analysis provided insights into the patterns of healing. CBCT-guided TAT could be adopted as an alternative for the conventional approach. (Clinical trial center and ethical board University Hospitals, KU Leuven: S55287; ClinicalTrials.gov Identifier: NCT02464202)