The purpose of this investigation was to evaluate systematically the literature concerning biopsy, MRI signal to noise quotient (SNQ) and clinical outcomes in graft-maturity assessment after autograft anterior cruciate ligament reconstruction (ACLR) and their possible relationships. Methods: The systematic review was reported and conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Studies through May 2019 evaluating methods of intra-articular ACL autograft maturity assessment were considered for inclusion. Eligible methods were histologic studies of biopsy specimens and conventional MRI studies reporting serial SNQ and/ or correlation with clinical parameters. Ten biopsy studies and 13 imaging studies, with a total of 706 patients, met the inclusion criteria. Biopsy studies show that graft remodeling undergoes an early healing phase, a phase of remodeling or proliferation and a ligamentization phase as an ongoing process even 1 year after surgery. Imaging studies showed an initial increase in SNQ, peaking at approximately 6 months, followed by a gradual decrease over time. There is no evident correlation between graft SNQ and knee stability outcome scores at the short- and long-term follow-up after ACLR. The remodeling of the graft is an ongoing process even 1 year after ACLR, based on human biopsy studies. MRI SNQ peaked at approximately 6 months, followed by a gradual decrease over time. Heterogeneity of the MRI methods and technical restrictions used in the current literature limit prediction of graft maturity and clinical and functional outcome measures by means of MRI graft SNQ after ACLR.