Background: Matrix-induced autologous chondrocyte implantation (MACI) has become an established technique for the repair of full-thickness chondral defects in the knee, although best patient outcomes appear limited by a lack of evidence-based knowledge on how to progressively increase postoperative weightbearing (WB) and rehabilitation exercises. Hypothesis: To determine the safety and efficacy of an accelerated WB regimen after MACI in the tibiofemoral joint. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Clinical and radiological assessments were performed in 28 knees at 12 months after MACI to the medial or lateral femoral condyle. Both rehabilitation interventions sought to protect the implant for an initial period and then incrementally increase load bearing. Under the “accelerated” (AR) protocol, patients reached full WB at 6 weeks after surgery compared with 8 weeks for what was considered to be the current “best practice” (CR) WB regimen based on previous research. Assessments included the Knee Injury and Osteoarthritis Outcome Score (KOOS), 36-Item Short Form Health Survey (SF-36), visual analog scale, 6-minute walk test, and active knee range of motion (ROM). High-resolution magnetic resonance imaging (MRI) was used to describe the quality and quantity of repair tissue via the assessment of pertinent parameters of graft repair as well as an MRI composite score. Results: Patients in both groups demonstrated significant improvement (P < .05) in all clinical measures over the preoperative and postoperative timeline from before surgery to 12 months after surgery. The AR group reported significantly better (P < .05) SF-36 physical component scores at 8 weeks and significantly greater (P < .05) KOOS quality of life scores at 6 and 12 months postoperatively. Although no differences (P > .05) were observed between the 2 groups for active knee ROM, the AR group did achieve full active knee extension as early as 4 weeks compared with the CR group at 12 weeks. There was no difference (P > .05) in graft quality as assessed by MRI (MOCART composite score: AR, 3.34; CR, 3.04), with no patients suffering any adverse effects from the implant up to 12 months, regardless of the rehabilitation protocol employed. Conclusion: The AR approach that reduced the length of time spent ambulating on crutches resulted in improved general physical function and quality of life and an earlier attainment of full active knee extension when compared with the CR approach. There were no graft complications ascertained through MRI. This regimen appears safe and may potentially speed up the recovery of normal gait function. A larger patient cohort and follow-up are required to observe long-term graft outcomes.