Objective. To evaluate the change in osteoarthritic (OA) knee cartilage volume over a two-year period with the use of magnetic resonance imaging (MRI) and to correlate the MRI changes with radiologic changes.Methods. Thirty-two patients with symptomatic knee OA underwent MRI of the knee at baseline and at 6, 12, 18, and 24 months. Loss of cartilage volumes were computed and contrasted with changes in clinical variables for OA and with standardized semiflexed knee radiographs at baseline at 1 and 2 years.Results. Progression of cartilage loss at all followup points was statistically significant (P < 0.0001), with a mean ؎ SD of 3.8 ؎ 5.1% for global cartilage loss and 4.3 ؎ 6.5% for medial compartment cartilage loss at 6 months, 3.6 ؎ 5.1% and 4.2 ؎ 7.5% at 12 months, and 6.1 ؎ 7.2% and 7.6 ؎ 8.6% at 24 months. Discriminant function analysis identified 2 groups of patients, those who progressed slowly (<2% of global cartilage loss; n ؍ 21) and those who progressed rapidly (>15% of global cartilage loss; n ؍ 11) over the 2 years of study. At baseline, there was a greater proportion of women (P ؍ 0.001), a lower range of motion (P ؍ 0.01), a greater circumference and higher level of pain (P ؍ 0.05) and stiffness in the study knee, and a higher body mass index in the fast progressor group compared with the slow progressor group. No statistical correlation between loss of cartilage volume and radiographic changes was seen.Conclusion. Quantitative MRI can measure the progression of knee OA precisely and can help to identify patients with rapidly progressing disease. These findings indicate that MRI could be helpful in assessing the effects of treatment with structure-modifying agents in OA.In people over the age of 60 years, osteoarthritis (OA) is a common cause of disability. Assessment of cartilage damage is important for monitoring disease progression and evaluating therapeutic response in OA. For many years, clinical studies of drug interventions in symptomatic knee OA have focused specifically on clinical parameters, such as pain and joint function, without assessing the effect of treatment on structural changes caused by the disease or the role of treatment in preventing cartilage degradation. Serial radiographs of affected joints appear to be a logical means of documenting the progression of OA over time (1), provided that a validated, reliable, and easily reproducible technique is used (2-5).