Our objective was to identify precise mechanical metrics of the proximal tibia which differentiated OA and normal knees. We developed subject-specific FE models for 14 participants (7 OA, 7 normal) who were imaged three times each for assessing precision (repeatability). We assessed various mechanical metrics (minimum principal and von Mises stress and strain as well as structural stiffness) across the proximal tibia for each subject. In vivo precision of these mechanical metrics was assessed using CV% . We performed parametric and non-parametric statistical analyses and determined Cohen's d effect sizes to explore differences between OA and normal knees. For all FE-based mechanical metrics, average CV% was less than 6%. Minimum principal stress was, on average, 75% higher in OA versus normal knees while minimum principal strain values did not differ. No difference was observed in structural stiffness. FE modeling could precisely quantify and differentiate mechanical metrics variations in normal and OA knees, in vivo. This study suggests that bone stress patterns may be important for understanding OA pathogenesis at the knee.