Background: Race-based practices in medical education and clinical care may exacerbate health inequities. Misguided use of race in popular point-of-care clinical decision-making tools like UpToDate® may promote harmful practices of race-based medicine. This article investigates the nature of mentions of Black/African American race in UpToDate®. Methods: We conducted a systematic content analysis of UpToDate® articles mentioning Black or African American race to assess for biological interpretations of racial categories. Following a simple text search for the terms "Black" and "African American" in UpToDate® on January 24 and March 19, 2020, respectively, removal of duplicates yielded an analytical sample of 208 documents. We adopted a deductive coding approach and systematically applied 16 a priori codes to all documents, refining the codebook to achieve a final inter-rater reliability of 0.91. We then developed these codes into two themes: (1) biologization of race and (2) racialized research and practice. Findings: Biologization of race occurred nearly universally across all documents (93.3%), with discussions of inherent physiological differences between racial groups and presentation of epidemiologic disparities without context emerging most frequently. Sixty-eight documents (32.7%) included codes related to racialized biomedical research and clinical practice, including references to racialized patterns of behavior and cultural practices, insufficient data on Black populations, research limiting study to a specific racial group, and race-based clinical practices guidelines. Interpretation: Our findings suggest that UpToDate® articles often inappropriately link Black race to genetics or clinical phenotype-without considering socio-structural variables or the health effects of structural racism-thus perpetuating a false narrative that race is inherently biological. UpToDate® articles may also promote unequal treatment by recommending race-based clinical practices. Such racial essentialism risks exacerbating racialized health inequities. Funding: The study is supported by the Health Policy Research Scholars Program, Robert Wood Johnson Foundation, Medical Scientist Training Program, National Institutes of Health, the National Science Foundation, the JPB Foundation, the Minnesota Population, the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), and the Center for Antiracism Research for Health Equity at the University of Minnesota.