BACKGROUND: Outcomes after anterior cruciate ligament reconstruction (ACLR) are not uniformly good and are worse among young female athletes. Developing better rehabilitation and return-to-sport training programs and evaluating their outcomes are essential. PURPOSE: (1) Test the effect of strength, agility, plyometric, and secondary prevention (SAPP) exercises with and without perturbation training (SAPP+PERT) on strength, hops, function, activity levels, and return-to-sport rates in young female athletes 1 and 2 years after ACLR and (2) compare 2-year functional outcomes and activity levels among young female athletes in the Anterior Cruciate Ligament Specialized Post-Operative Return-to-Sports (ACL-SPORTS) trial to homogeneous cohorts who completed criterion-based postoperative rehabilitation alone (Multicenter Orthopaedic Outcomes Network (MOON)) and in combination with extended preoperative rehabilitation (Delaware-Oslo). STUDY DESIGN: Randomized controlled trial, level of evidence, 1; and cohort study, level of evidence, 3. METHODS: A total of 40 level 1 and level 2 female athletes were enrolled after postoperative impairment resolution 3 to 9 months after primary ACLR. Participants were randomized to 10 SAPP or SAPP+PERT sessions and were tested 1 and 2 years after ACLR on quadriceps strength, hop tests, functional outcomes, and return-to-sport rates. Participants were then compared with homogeneous cohorts of young (< 25 years) female athletes who completed criterion-based postoperative rehabilitation alone (MOON) and in combination with extended preoperative rehabilitation (Delaware-Oslo) on 2-year functional outcomes. RESULTS: No significant or meaningful differences were found between SAPP and SAPP+PERT, so groups were collapsed for comparison with the other cohorts. At 2-year follow-up, ACL-SPORTS had the highest scores (p < 0.01) on the Marx activity rating scale (ACL-SPORTS 13.5 +/- 3.3; Delaware-Oslo 12.5 +/- 2.7; MOON 10.6 +/- 5.1); International Knee Documentation Committee Subjective Knee Evaluation Form (96 +/- 7, 92 +/- 9, and 84 +/- 14, respectively); and Knee injury and Osteoarthritis Outcome Score (KOOS) subscales for Pain (98 +/- 4, 94 +/- 9, and 90 +/- 10, respectively), Symptoms (94 +/- 6, 90 +/- 9, and 83 +/- 14, respectively), Activities of Daily Living (100 +/- 1, 99 +/- 4, and 96 +/- 7, respectively), Sports and Recreation (94 +/- 8, 86 +/- 15, and 82 +/- 17, respectively), and Quality of Life (89 +/- 14, 78 +/- 18, and 76 +/- 19, respectively). The Patient Acceptable Symptom State threshold on the KOOS-Sports and Recreation was achieved by 100% of the ACL-SPORTS cohort compared with 90% of Delaware-Oslo and 78% of MOON (p = 0.011). CONCLUSION: Although perturbation training provided no added benefit, 10 sessions of return-to-sport training, compared with criterion-based postoperative rehabilitation alone, yielded statistically significant and clinically meaningfully higher 2-year functional outcomes among young, high-level female athletes after ACLR. REGISTRATION: NCT01773317 (ClinicalTrials.gov identifier).

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