In individuals without radiographic knee osteoarthritis (KOA), we investigated whether MRI-defined KOA at baseline was associated with incident radiographic and symptomatic disease during up to 11 years of follow-up. Osteoarthritis Initiative participants without tibiofemoral radiographic KOA at baseline were assessed for MRI-based tibiofemoral cartilage damage, osteophyte presence, bone marrow lesions, and meniscal damage/extrusion. We defined MRI KOA using alternative, reported definitions (Def A and Def B). Kellgren-Lawrence (KL) grade, joint space narrowing (JSN), and frequent knee symptoms (Sx) were assessed at baseline, 1-, 2-, 3-, 4-, 6-, 8-, and 10/11-year follow-up visits. Incident tibiofemoral radiographic KOA (outcome) was defined as (1) KL ≥ 2, (2) KL ≥ 2 and JSN, or (3) KL ≥ 2 and Sx. Adjusted Cox proportional hazards regression models examined associations of baseline MRI-defined KOA (Def A and Def B) with incident outcomes during up to 11 years of follow-up. Among 1621 participants [mean age=58.8 (SD=9.0) years, mean BMI=27.2 (4.5) kg/m2, 59.5% women], 17% had MRI-defined KOA by Def A and 24% by Def B. Baseline MRI-defined KOA was associated with incident KL ≥ 2 [odds ratio=2.94 (95% CI=2.34-3.68) for Def A and 2.44 (95% CI=1.97-3.03) for Def B]. However, a substantial proportion of individuals with baseline MRI-defined KOA did not develop incident KL ≥ 2 during follow-up (59% for Def A and 64% for Def B). Findings were similar for the other two outcomes. Current MRI definitions of KOA do not adequately identify knees that will develop radiographic and symptomatic disease.