Image‐based assessments of quadriceps muscle size facilitate examination of structural changes after anterior cruciate ligament (ACL) injury and reconstruction (ACLR). Understanding the effects of ACLR on muscle size measures may aid in clarifying the contribution of quadriceps atrophy toward quadriceps strength. The purpose of this study was to systematically review the literature examining the effects of ACLR on quadriceps muscle volume and cross‐sectional area (CSA). An online database search was conducted using Web of Science, SportDISCUS, PubMed (Medline), CINHAL (EBSCO), and Cochrane Library limited to articles published after January 1, 1980. Means and standard deviations were extracted for the ACLR limb and the contralateral limb, and sample characteristics from relevant articles. Magnitude of between limb differences were assessed using pooled effect sizes (Hedge's g) and 95% confidence intervals. Eleven articles (five CSA, six muscle volume) were included in this systematic review. Included studies reported negative effective sizes, indicating that the ACLR limb was smaller in CSA or muscle volume compared with the contralateral limb; however, 36% of the included articles reported meaningful difference between the limbs. Quadriceps atrophy may occur following ACL injury and persist after rehabilitation, however, the magnitude of these reductions may not be clinically meaningful and may only partially explain the persistent quadriceps weakness that is ubiquitous among this patient population. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:598–608, 2020