The association between proximal tibiofibular joint (PTFJ) and knee osteoarthritis (OA) has been understudied. The objective of this study was to determine whether the morphology of PTFJ has predictive value for the risk of total knee replacement (TKR). Case knees from Osteoarthritis Initiative participants with TKR at 24-60 months follow up (cases) were 1:1 matched with control knees (no TKR throughout 60 months) by baseline age, sex, and Kellgren-Lawrence grade. PTFJ morphological parameters, including coronal inclination angle (angle alpha), sagittal inclination angle (angle beta), fibular contacting area (S), load-bearing area (S tau), lateral stress-bolstering area (S phi), and posterior stress-bolstering area (S upsilon) were assessed using coronal and sagittal magnetic resonance imaging (MRI), respectively. Associations of the morphological measures at baseline and the time point before TKR (T-0) and their changes with TKR risks were examined using conditional logistic regression analyses. Two hundred and twenty-three knees of 193 participants received TKR between 12 and 60 months and therefore were matched with 223 control knees. Of these, 173 paired knees had MRI readings available both at baseline andT(0)time point. While baseline angle alpha was positively associated with TKR risk, other measures at baseline and all measures atT(0)were not significantly associated with TKR risk. Changes inS,S tau, andS upsilon were significantly and negatively associated with the risk of TKR (Delta S, odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.19-0.76; Delta S tau, OR = 0.37, 95% CI: 0.16-0.87; Delta S upsilon, OR = 0.22, 95% CI: 0.08-0.62, respectively). This data shows that morphological changes of PTFJ predict the risk of TKR, suggesting PTFJ may play a role in knee OA.