The investigative team has completed recent studies showing that essential amino acid (EAA) supplementation attenuates quadriceps atrophy and accelerates the return of functional mobility following TKA. For patients on EAA, quadriceps atrophy was only -6% and -3% in the operative and non-operative quadriceps, respectively, 6 wks after TKA, but -18% and -10%, respectively, in patients on Placebo, a threefold difference. Of clinical relevance, the patients on EAA were able to maintain strength and demonstrated an accelerated return of functional mobility vs. Placebo 6 wks post-TKA. Positive changes at the cellular level are likely responsible for the reduction in muscle loss and preservation of strength, and to explain the acceleration of the return of functional mobility. As such, we hypothesize that twice-daily ingestion of 20 g of EAA from 1 wk before to 6 wks after TKA will increase basal rates of muscle protein synthesis via inactivation of catabolic signaling (FoxO3a), and up-regulation of anabolic and cyto-protective proteins. We also propose that short-term atrophy prevention and accelerated return of functional mobility will translate into long-term (6 mo and 1 yr post-TKA) structural and functional adaptations, leading to improved quality of life in TKA patients with EAA supplementation vs. Placebo.