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Abstract Economic costs of osteoarthritis (OA) are considerable. However, there are no clinical tools to predict the progression of OA or guide patients to a correct treatment for preventing OA. We tested the ability of our cartilage degeneration algorithm to predict the subject-specific development of OA and separate groups with different OA levels. The algorithm was able to predict OA progression similarly with the experimental follow-up data and separate subjects with radiographical OA (Kellgren-Lawrence (KL) grade 2 and 3) from healthy subjects (KL0). Maximum degeneration and degenerated volumes within cartilage were significantly higher (p < 0.05) in OA compared to healthy subjects, KL3 group showing the highest degeneration values. Presented algorithm shows a great potential to predict subject-specific progression of knee OA and has a clinical potential by simulating the effect of interventions on the progression of OA, thus helping decision making in an attempt to delay or prevent further OA symptoms.