Objective: To determine if qualitative and quantitative measures of prefemoral fat pad (PFP) and quadriceps fat pad (QFP) are associated with incident radiographic osteoarthritis (iROA) over 4 years in the Osteoarthritis Initiative (OAI) study. Design: Participants in this nested caseecontrol study were selected from the OAI study with knees that had Kellgren Lawrence grades (KLG) of 0 or 1 at baseline. Case knees were defined by iROA (KLG 2) over 4 years. Control knees without iROA were matched 1:1 with case knees. Magnetic resonance images (MRIs) were read at P0 (time of onset of iROA), P-1 (1 year prior to P0) and baseline, and used to assess PFP (i.e., prefemoral hyperintensity alteration, patellofemoral hyperintensity alteration, maximum axial area) and QFP (i.e., hyperintensity alteration, mass effect, maximum axial area). Conditional logistic regression analyses were performed to study the associations between PFP/QFP measures and iROA, after adjustment for covariates. Results: 354 case knees with iROA were matched to 354 control knees. 66.9% of the participants were female, with an average age of 60.1 years. PFP prefemoral hyperintensity alteration measured at three time points (OR [95%CI]: 1.46 [1.18e1.82], 1.50 [1.20e1.88], 1.52 [1.22e1.89] respectively), PFP maximum axial area (OR [