BACKGROUND: Knee osteoarthritis (OA) and frailty are two conditions that are associated with functional limitation and disability in elders, yet their relation to one another is not known. METHODS: We included participants from two large, multicenter studies enriched with community dwelling older adults with knee OA (Multicenter Osteoarthritis Study and Osteoarthritis Initiative). Knee OA was defined radiographically (ROA) and symptomatically (SOA). Frailty was defined using the Study of Osteoporotic Fracture index as the presence of ≥2 of the following: (i) weight loss >5% between two consecutive visits; (ii) inability to arise from chair five times without support; (iii) poor energy. Cross-sectional and longitudinal associations of knee OA with prevalent and incident frailty, respectively, were examined using binomial regression with robust variance estimation, adjusting for potential confounders. RESULTS: In the cross-sectional analyses, frailty was more prevalent among participants with ROA (4.39% vs 2.77%; PR 1.60 [1.07, 2.39]) and SOA (5.88% vs 2.79%; PR 1.92 [1. 35, 2.74]) compared with those without ROA or SOA, respectively. In the longitudinal analyses, risk of developing frailty was greater among those with ROA (4.73% vs 2.50%; RR 1.45 [0.91, 2.30]) and SOA (6.30% vs 2.83%; RR 1.66 [1.11, 2.48]) than those without ROA or SOA, respectively. CONCLUSIONS: Knee OA is associated with greater prevalence and risk of developing frailty. Understanding the mechanisms linking these two common conditions of older adults would aid in identifying novel targets for treatment or prevention of frailty.