BACKGROUND: Racial disparities in renal transplantation outcomes have been documented with inferior allograft survival among African Americans compared with non-African Americans. These differences have been attributed to a variety of factors, including immunologic hyperresponsiveness, socioeconomic status, compliance, HLA matching, and access to care. The purpose of this study was to examine both immunologic and nonimmunologic risk factors for allograft loss with a goal of defining targeted strategies to improve outcomes among African Americans. STUDY DESIGN: We retrospectively analyzed all primary deceased-donor adult renal transplants (n = 2,453) at our center between May 1987 and December 2004. Analysis included the impact of recipient and donor characteristics, HLA typing, and immunosuppressive regimen on graft outcomes. Data were analyzed using standard Kaplan-Meier actuarial techniques and were explored with nonparametric and parametric methods. Multivariable analyses in the hazard-function domain were done to identify specific risk factors associated with graft loss. RESULTS: The 1-year allograft survival in recipients improved substantially throughout the study period, and 3-year allograft survival also improved. Risk factor analyses are shown by type of allograft and according to specific time periods. Risk of immunologic graft loss (acute rejection) was most prominent during the early phase. During late-phase, immunologic risk persists (chronic rejection), but recurrent disease, graft quality, and recipient's comorbidities have an increasingly greater role. CONCLUSIONS: Advances in immunosuppression regimens have contributed to allograft survival in both early and late (constant) phases throughout all eras, but improvement in longterm outcomes for African Americans continues to lag behind non-African Americans. The disparity in renal allograft loss between African Americans and non-African Americans over time indicates that beyond immunologic risk, the impact of nonimmunologic variables, such as time on dialysis pretransplantation, diabetes, and access to medical care, can be key issues.