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Background: When stable osteochondritis dissecans (OCD) lesions of the femoral condyle in a skeletally immature patient fail to heal with nonoperative methods, the standard of care treatment is condylar OCD drilling. Two primary OCD drilling techniques have been described, but no prospective studies have compared their relative effectiveness. Purpose/Hypothesis: The purpose of this study was to compare the healing and function after transarticular drilling (TAD) with that after retroarticular drilling (RAD). It was hypothesized that there would be no difference in rate or time to healing, rate or time to return to sports, patient-reported outcomes (PROs), or secondary OCD-related surgery. Study Design: Randomized controlled clinical trial; Level of evidence, 1. Methods: Skeletally immature patients with magnetic resonance imaging–confirmed stable OCD lesions of the medial femoral condyle who did not demonstrate substantial healing after a minimum of 3 months of nonoperative treatment were prospectively enrolled by 1 of 17 surgeon-investigators at 1 of 14 centers. Patients were randomized to the TAD or RAD group. Tourniquet time, fluoroscopy time, and complications were compared between the treatment groups. Postoperatively, serial radiographs were obtained every 6 weeks to assess healing, and PROs were obtained at 6 months, 12 months, and 24 months. Results: A total of 91 patients were included, consisting of 51 patients in the TAD and 40 patients in the RAD group, who were similar in age, sex distribution, and 2-year PRO response rate. Tourniquet time and fluoroscopy time were significantly shorter with TAD (mean, 38.1 minutes and 0.85 minutes, respectively) than RAD (mean, 48.2 minutes and 1.34 minutes respectively) (P =.02; P =.004). In the RAD group, chondral injury from K-wire passage into the intra-articular space was reported in 9 of 40 (22%) patients, but no associated postoperative clinical sequelae were identified in these patients. No significant differences between groups were detected in follow-up Pediatric–International Knee Documentation Committee, Lysholm, Marx Activity Scale, or Knee injury and Osteoarthritis Outcome Score Quality of Life scores. Healing parameters were superior at 6 months and 12 months in the TAD group, compared with the RAD group, and secondary OCD surgery occurred in 4% of patients who underwent TAD and 10% of patients who underwent RAD (P =.40). Patients in the TAD group returned to sports earlier than those in the RAD group (P =.049). Conclusion: TAD showed shorter operative time and fluoroscopy time and superior healing parameters at 6 and 12 months, but no differences were seen in 24-month healing parameters or PROs at all follow-up time points, when compared with RAD. Registration: NCT01754298 (ClinicalTrials.gov identifier). [ABSTRACT FROM AUTHOR]