Following total knee arthroplasty (TKA) patients exhibit significant impairment in quadriceps strength and function1. Muscle activation deficits and atrophy contribute to the significant quadriceps weakness exhibited by these patients2. Activation deficits, or the inability to recruit available muscle fibers, can impede the success of traditional strengthening paradigms. This study monitored recovery of the quadriceps after TKA to further understand the morphological and neural mechanisms of long-term quadriceps weakness. 41 patients were tested 9±5 days before unilateral TKA and 1, 3 and 12 months after TKA. Patients completed 6 weeks of outpatient physical therapy. A burst superimposition test on a maximum voluntary isometric contraction (MVIC) was used to measure quadriceps strength and activation2. Magnetic resonance imaging (MRI) determined maximal cross-sectional area (CSA) 2. Differences in quadriceps variables between limbs over time were analyzed using a repeated 2-way ANOVA and paired t-tests for post hoc analysis. Linear regression determined relative contributions to quadriceps strength. Significant differences between limbs and over time were found in quadriceps MVIC (F=138.87, p<0.001; F=51.83, p<0.001), activation (F=20.01, p<0.001; F=8.43, p<0.001), and CSA (F=58.86, p<0.001; F=13.46, p<0.001). The surgical limb had lower MVIC both before TKA (t=-5.53, p<0.001) and 1 (t=-13.59, p<0.001) and 3 (t=-18.57, p<0.001) months after TKA. The surgical limb had lower CSA both before TKA (t=-4.77, p<0.001) and 1 (t=-8.62, p<0.001) and 3 (t=-7.16, p<0.001) months after TKA. No differences in activation were evident before TKA (t=-1.27, p=0.211) or at 3 (t=-1.85, p=0.07) months however, the surgical limb had lower activation 1 (t=-5.54, p<0.001) month post-TKA. One year after TKA, no significant differences were found between limbs in quadriceps MVIC (t=-0.33, p=0.747), CSA (t=-1.66, p=0.117), or activation (t=0.90, p=0.0.380). Together, activation and CSA explained 69% of the variance in involved quadriceps strength (R2=0.77, p<0.001) at 3 months. When preoperative strength was added to the equation, 77% of the variance in 3 month involved MVIC was explained. Activation and CSA explained 62% of the variance in involved quadriceps strength 1 year post-TKA (R2=0.62, p<0.05) however, preoperative strength was still the single strongest predictor of 1 year involved strength (R2=0.72, p<0.001). Deficits in muscle strength, activation, and CSA persisted 3 months after TKA, when the majority of patients are discharged from formal physical therapy. Complete recovery of quadriceps strength and morphology was evident 1 year postoperatively. Preoperative strength was the best predictor of long-term strength outcomes. Full quadriceps recovery may be limited by delaying surgery until patients are completely debilitated by pain. Preoperative strengthening may optimize benefit from surgery.