Abstract Introduction Patient preferences contribute to marked racial disparities in the utilization of total knee replacement (TKR). The objectives of this study were to identify the determinants of knee osteoarthritis (OA) patients’ preferences regarding TKR by race and to identify the variables that may mediate racial differences in willingness to undergo TKR. Methods Five hundred fourteen White (WH) and 285 African-American (AA) patients with chronic knee pain and radiographic evidence of OA participated in the study. Participants were recruited from the community, an academic medical center, and a Veterans Affairs hospital. Structured interviews were conducted to collect socio-demographics, disease severity, socio-cultural determinants, and treatment preferences. Logistic regression was performed, stratified by race, to identify determinants of preferences. Clinical and socio-cultural factors were entered simultaneously into the models. Stepwise selection identified factors for inclusion in the final models (p