The objective of this study was to describe the rate of change in knee cartilage volume over 4.5 years in subjects with symptomatic knee osteoarthritis (OA) and to determine factors associated with cartilage loss. One hundred and five subjects were eligible for this longitudinal study. Subjects' tibial cartilage volume was assessed by magnetic resonance imaging (MRI) at baseline, at 2 years and at 4.5 years. Of 105 subjects, 78 (74%) completed the study. The annual percentage losses of medial and lateral tibial cartilage over 4.5 years were 3.7 ± 4.7% (mean ± SD; 95% confidence interval 2.7 to 4.8%) and 4.4 ± 4.7% (mean ± SD; 95% confidence interval 3.4 to 5.5%), respectively. Cartilage volume in each individual seemed to track over the study period, relative to other study participants. After multivariate adjustment, annual medial tibial cartilage loss was predicted by lesser severity of baseline knee pain but was independent of age, body mass index and structural factors. No factors specified a priori were associated with lateral cartilage volume rates of change. Tibial cartilage declines at an average rate of 4% per year in subjects with symptomatic knee OA. There was evidence to support the concept that tracking occurs in OA. This may enable the prediction of cartilage change in an individual. The only significant factor affecting the loss of medial tibial cartilage was baseline knee pain, possibly through altered joint loading.