Background: Total knee arthroplasty (TKA) is a successful procedure for people with end-stage knee osteoarthritis (KOA). However, nearly half of people following unilateral TKA will require a contralateral TKA within 10 years. It is unclear the mechanism(s) of the contralateral KOA progression. However, as the population undergoing TKA continues to get younger and more active, preserving the integrity of both knee joints is essential for long-term outcomes. Objective: To identify clinical predictors of radiographic KOA progression in the contralateral knee post-TKA. Methods: Forty people with TKA participated in this longitudinal observational study. Participants were defined as either non-progressors (no change) or progressors (worsening) based on the Kellgren-Lawrence (KL) scale or knee Joint Space Width (JSW) of the medial and lateral compartments from pre- to >6 years post-TKA. Clinical predictors including age, sex, BMI, knee pain, range of motion, knee girth, six-minute walk test, timed up and go, stair climbing test, and quadriceps strength collected at 6-24 months post-TKA. Between group differences were analyzed using logistic regression and t-tests. Results: Based on the KL method, 25 participants (62.5%) were classified into the progressor group at 7.6+1.96 years post-TKA. While based on the JSW, 29 participants (78%) were classified into the progressor group at 7.3+1.0 years post-TKA. Contralateral quadriceps strength was significantly higher in the non-progressor group compared to the progressor group (p=0.033). Contralateral quadriceps strength was also a significant predictor of KOA progression (p=0.047). No other clinical predictor was related to contralateral KOA progression post-TKA. Conclusions: Contralateral KOA progression was common in people following primary post-TKA, despite being asymptomatic at baseline. Quadriceps strength of the contralateral limb was significant as predicting KOA progression post-TKA. These findings will help clinicians better educate patients and develop targeted strengthening interventions for improving contralateral joint health in people post-TKA.