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Return-to-activity (RTA) assessments are commonly administered after anterior cruciate ligament reconstruction (ACLR) to manage the patient's postoperative progressions back to activity. To date, few data are available on the clinical utility of these assessments to predict patient outcomes such as secondary anterior cruciate ligament (ACL) injury once the athlete has returned to activity. To identify the measures of patient function at 6 months post-ACLR that best predict RTA and second ACL injury at a minimum of 2 years after ACLR. Prospective cohort study. Laboratory. A total of 234 patients with primary, unilateral ACLR completed functional assessments at approximately 6 months post-ACLR. Of these, 192 (82.1%) completed follow-up at ≥2 years post-ACLR. The 6-month functional assessments consisted of patient-reported outcomes, isokinetic knee-flexor and -extensor strength, and single-legged hopping. We collected RTA and secondary ACL injury data at ≥2 years after ACLR. Of the patients who were able to RTA (n = 155), 44 (28.4%) had a subsequent ACL injury, 24 (15.5%) to the ipsilateral graft ACL and 20 (12.9%) to the contralateral ACL. A greater proportion of females had a secondary injury to the contralateral ACL (15/24, 62.5%), whereas a greater proportion of males reinjured the ipsilateral ACL graft (15/20, 75.0%; P =.017). Greater knee-extension symmetry at 6 months increased the probability of reinjury (B = 0.016, P =.048). Among patients with RTA at < 8 months, every 1% increase in quadriceps strength symmetry at 6 months increased the risk of reinjury by 2.1% (B = 0.021, P =.05). Among patients with RTA at >8 months, every month that RTA was delayed reduced the risk of reinjury by 28.4% (B = –0.284, P =.042). Descriptive statistics of patient function stratified between the early and delayed RTA groups can be found in the Supplemental Table (available online at http://dx.doi.org/10.4085/1062-6050-0407.20.S1). Patients with more symmetric quadriceps strength at 6 months post-ACLR were more likely to experience another ACL rupture, especially those who returned to sport at < 8 months after the index surgery. Clinicians should be cognizant that returning high-functioning patients to activity at < 8 months post-ACLR may place them at an increased risk for reinjury. [ABSTRACT FROM AUTHOR]