Purpose: The Medicare Prescription Drug Benefit (Part D) program debuted in January 2006. We ascertained the sociodemographic and health characteristics of Blacks and Whites who enrolled in the early stages of the program. Design and Methods: Data were collected between April 2006 and October 2007 from an ongoing population-based biracial study of older adults. Results: We interviewed 2,694 subjects, 1,784 Blacks and 910 Whites, of whom 40% and 35% reported to have enrolled in Medicare Part D, respectively. Among Blacks, those who enrolled were more likely to be female, unmarried, have less education and income, more medical conditions, greater physical disability, and poorer physical function than Blacks who did not enroll. Among Whites, enrollees were older, female, and had less education compared with White nonenrollees. In the multivariate analyses, older age, female, being married, lower income, worse physical function, and better cognitive function were associated with program enrollment. Implications: These results indicate that the profiles of adults who initially enrolled in Medicare Part D differed somewhat by race. Program enrollment among Blacks was largely driven by financial need and poor health; however, among Whites, there was no such discernible pattern of enrollment. In addition, we observed a knowledge gap among Black nonenrollees who reported that they were unaware of and confused by the program and plans. The findings suggest that Medicare Part D may serve different needs in different subpopulations. The long-term impact of these differential program profiles on Black–White health disparities remains uncertain and requires continued monitoring.