ObjectiveThe purpose of this study is to delineate cross-sectional associations between qualitative and quantitative measures of the infrapatellar fat pad (IPFP) and knee symptoms, structure, kinematics, and kinetics in older adults. MethodsNinety eligible subjects (90 knees, mean age 54.0 years, 68.9% female) were examined at our centre. We used T2-weighted fat-suppressed magnetic resonance imaging (MRI) to evaluate signal intensity alteration, maximum sagittal area, and depth of the IPFP. Symptomatic osteoarthritis (SOA) was a pain subscale score greater than 0 on the Western Ontario McMaster Osteoarthritis Index. A Kellgren-Lawrence grade ≥ 2 identified incident radiographic osteoarthritis (iROA). Three-dimensional gait data were employed to analyze knee joint kinematics and kinetics. Correlation and regression analyses assessed associations between IPFP measurements and SOA, iROA, kinematics, and kinetics. ResultsThere were strong and positive associations between IPFP signal intensity alteration and both SOA and iROA in multivariable regression analyses [OR (95% CI): 2.849 (1.440 to 5.636), 2.356 (1.236 to 4.492), respectively]. Conversely, a significant negative correlation was observed between IPFP maximum area and flexion angle [B (95%CI): -1.557 (-2.549 to -0.564)]. Moreover, adjusting for covariates did not reveal any significant correlation between IPFP parameters and other indicators (P > 0.05, respectively). ConclusionIPFP signal intensity alteration and area were associated with knee clinical symptoms, structural abnormalities, and flexion angle in adults over 40, respectively. These findings suggest that IPFP may be a crucial imaging biomarker in early and middle knee osteoarthritis.