Background: Numerous graft options are available when undertaking anterior cruciate ligament (ACL) reconstruction (ACLR), although a lack of high-quality evidence exists comparing quadriceps (QT) and hamstring (HT) autografts. Purpose: To investigate patient outcomes in patients undergoing HT versus QT ACLR. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: After recruitment and randomization, 112 patients (HT = 55; QT = 57) underwent ACLR. Patients were assessed pre- and postoperatively (6 weeks and 3, 6, 12, and 24 months), with a range of patient-reported outcome measures (PROMs), graft laxity (KT-1000 arthrometer; primary outcome variable), active knee flexion and extension range of motion (ROM), peak isokinetic knee extensor and flexor strength, and a 6-hop performance battery. Limb symmetry indices (LSIs) were calculated for strength and hop measures. Secondary procedures, ACL retears, and contralateral ACL tears were reported. Results: All PROMs and knee ROM measures significantly improved (P < .0001), and no other group differences (P > .05) were observed—apart from the Anterior Cruciate Ligament Return to Sport after Injury (ACL-RSI) score, which was significantly better in the HT group at 3 (P = .008), 6 (P = .010), and 12 (P = .014) months. No significant changes were observed in side-to-side laxity from 6 to 24 months (P = .105), and no group differences were observed (P = .487) at 6 (HT mean, 1.2; QT mean, 1.3), 12 (HT mean, 1.1; QT mean, 1.3), and 24 (HT mean, 1.1; QT mean, 1.2) months. While the HT group demonstrated significantly greater (P < .05) quadriceps strength LSIs at 6 and 12 months, the QT group showed significantly greater (P < .05) hamstring strength LSIs at 6, 12, and 24 months. The HT group showed significantly greater (P < .05) LSIs for the single horizontal (6 months), lateral (6 and 12 months), and medial (6 months) hop tests for distance. Up until 24 months, 1 patient (QT at 22 months) had a retear, with 2 contralateral ACL tears (QT at 19 months; HT at 23 months). Secondary procedures included 5 in the HT group (manipulation under anesthesia, notch debridement, meniscal repair, and knee arthroscopy for scar tissue) and 6 in the QT group (notch debridement, meniscal repair, knee arthroscopy for scar tissue, tibial tubercle transfer, and osteochondral autologous transplantation). Conclusion: Apart from the ACL-RSI, the 2 autograft groups compared well for PROMs, knee ROM, and laxity. However, greater hamstring strength LSIs were observed for the QT cohort, with greater quadriceps strength (and hop test) LSIs in the HT cohort. The longer-term review will continue to evaluate return to sports and later-stage reinjury between the 2 graft constructs. Registration: ACTRN12618001520224p (Australian New Zealand Clinical Trials Registry).