Objectives. Cartilage defects are present in subjects with knee osteoarthritis (OA). Although they are often present in healthy subjects, there is little data on the natural history of cartilage defects. The aim of this study was to examine the change in cartilage defects over 2 yr and to identify factors associated with this change. Methods. One hundred and twenty-four healthy subjects underwent magnetic resonance imaging of their dominant knee at baseline and follow-up. Cartilage defects were scored (0–4) at five sites. Bone size was determined at medial and lateral tibial plateau and patella. Height, weight, body mass index and physical activity were measured by standard protocols. Results. Eighty-six subjects completed the study. The mean cartilage defect score of each tibiofemoral compartment increased over time. However, medial and lateral tibiofemoral defect score decreased in 5% of the subjects. Cartilage defects were more likely to progress in males than females in each individual compartment (P