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Wear-related complications remain a major issue after unicompartmental arthroplasty. We used a computational model to predict knee wear generated in vitro under diverse conditions. Inverse finite element analysis of 2 different total knee arthroplasty designs was used to determine wear factors of standard and highly crosslinked polyethylene by matching predicted wear rates to measured wear rates. The computed wear factor was used to predict wear in unicompartmental components. The articular surface design and kinematic conditions of the unicompartmental and tricompartmental designs were different. Predicted wear rate (1.77 mg/million cycles) was very close to experimental wear rate (1.84 mg/million cycles) after testing in an AMTI knee wear simulator. Finite element analysis can predict experimental wear and may reduce the cost and time of preclinical testing.