OBJECTIVE:Inflammation is known to be strongly associated with knee pain in osteoarthritis. The infrapatellar fat pad represents a potential source of proinflammatory cytokines. Yet the relationship between infrapatellar fat pad morphology and osteoarthritis symptoms is unclear. METHODS:Here we investigate quantitative imaging parameters of infrapatellar fat pad morphology between painful versus contralateral pain-free legs of subjects with unilateral knee pain and patients with chronic knee pain versus those of matched pain-free control subjects. A total of 46 subjects with strictly unilateral frequent knee pain and bilateral radiographic osteoarthritis (Kellgren/Lawrence grade 2/3) were drawn from the Osteoarthritis Initiative. Further, 43 subjects with chronic knee pain over 4 years and 43 matched pain-free controls without pain over this period were studied. Infrapatellar fat pad morphology (volume, surface area, and depth) was determined by manual segmentation of sagittal magnetic resonance images. RESULTS:No significant differences in infrapatellar fat pad morphology were observed between painful versus painless knees of persons with strictly unilateral knee pain (mean difference -0.7% (95% confidence interval [95% CI] -0.6, 0.9; P = 0.64) or between chronically painful knees versus matched painless controls (-2.1% [95% CI -2.2, 1.1]; P = 0.51). CONCLUSION:Independent of the ambiguous role of the infrapatellar fat pad in knee osteoarthritis (a potential source of proinflammatory cytokines or a mechanical shock absorber), the size of the infrapatellar fat pad does not appear to be related to knee pain.