BACKGROUND: Preventing worsening osteoarthritis (OA) in persons with early OA is a major treatment goal. We evaluated if different early OA definitions yielded enough cases of worsening OA within 2-5 years to make trial testing treatments feasible. METHODS: We assessed different definitions of early OA using data from Multicenter Osteoarthritis (MOST) Study participants who were followed up longitudinally. We defined early OA as having at least minimal knee pain (WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain ≥3/20) with different levels of pre-radiographic OA. For MRI, we required knee pain and used MRI definitions with combinations of cartilage damage, osteophytes, bone marrow lesions and meniscus damage. The primary outcome, worsening OA at 2 or 5 years, combined structural (Kellgren and Lawrence grade ≥2 with joint space narrowing ≥1) and symptom (WOMAC pain ≥6 with increase ≥2 from baseline) outcomes. We also examined structural and symptom outcomes separately. RESULTS: For worsening OA at 2 years, we included 750 participants (mean age 65 years, 60% female, 90% white, mean body mass index 29.2 kg/m CONCLUSION: Most knees with early OA are stable and do not progress. Some painful knees experience worse pain but not structural progression and vice versa. Trial testing treatments to prevent OA illness or disease will be challenging.