Context: Study of muscle volumes in patients after anterior cruciate ligament (ACL) injury and reconstruction (ACL-R) is largely limited to cross-sectional assessment of the thigh musculature, which may inadequately describe posttraumatic and postsurgical muscle function. No studies have prospectively examined the influence of ACL injury and reconstruction on lower-extremity muscle volumes. Objective: Assess magnetic resonance imaging-derived lower-extremity muscle volumes, and quantify quadriceps strength and activation in patients following ACL injury and reconstruction. Design: Prospective case series. Setting: Research laboratory and magnetic resonance imaging facility. Patients (or Other Participants): Four patients (2 men and 2 women; age = 27.4 (7.4) y, height = 169.2 (8.1) cm, and mass = 74.3 (18.5) kg) scheduled for ACL-R. Intervention(s): Thirty-five muscle volumes were obtained from a bilateral lower-extremity magnetic resonance imaging before and after ACL-R. Main Outcome Measures: Muscle volumes expressed relative to (1) a normative database presurgery and postsurgery, (2) limb symmetry presurgery and postsurgery, and (3) percentage change presurgery to postsurgery. Quadriceps function was quantified by normalized knee extension maximal voluntary isometric contraction torque and central activation ratio. Results: Involved vastus lateralis and tibialis anterior were consistently smaller than healthy individuals (z < −1 SD) presurgery and postsurgery in all patients. Involved rectus femoris and vastus lateralis were more than 15% smaller than the contralateral limb presurgery, whereas the involved rectus femoris, gracilis, vastus medialis, vastus intermedius, and vastus lateralis muscle volumes exceeded 20% asymmetry postoperatively. Involved gracilis and semitendinosus atrophied more than 30% from presurgery to postsurgery. Involved maximal voluntary isometric contraction torque and central activation ratio increased by 12.7% and 12.5%, respectively, yet strength remained 33.2% asymmetric postsurgery. Conclusions: Adaptations in lower-extremity muscle volumes are present following ACL injury and reconstruction. Anterior thigh and shank muscles were smaller than healthy individuals, and large asymmetries in quadriceps volumes were observed presurgery and postsurgery. Selective atrophy of the semitendinosus and gracilis occurred following surgery. Volumetric deficits of the quadriceps musculature may exist despite improvements in muscle strength and activation.