Numerous factors are known to impact on patient survival after renal transplantation. Recent studies have confirmed a survival advantage for renal transplant patients over those waiting on dialysis. We aimed to investigate the hypothesis that longer waiting times are more deleterious than shorter waiting times, that is, to detect a "dose effect" for waiting time. We analyzed 73,103 primary adult renal transplants registered at the United States Renal Data System Registry from 1988 to 1997 for the primary endpoints of death with functioning graft and death-censored graft failure by Cox proportional hazard models. All models were corrected for donor and recipient demographics and other factors known to affect outcome after kidney transplantation. A longer waiting time on dialysis is a significant risk factor for death-censored graft survival and patient death with functioning graft after renal transplantation (P < 0.001 each). Relative to preemptive transplants, waiting times of 6 to 12 months, 12 to 24 months, 24 to 36, 36 to 48, and over 48 months confer a 21, 28, 41, 53, and 72% increase in mortality risk after transplantation, respectively. Relative to preemptive transplants, waiting times of 0 to 6 months, 6 to 12 months, 12 to 24 months, and over 24 months confer a 17, 37, 55, and 68% increase in risk for death-censored graft loss after transplantation, respectively. Longer waiting times on dialysis negatively impact on post-transplant graft and patient survival. These data strongly support the hypothesis that patients who reach end-stage renal disease should receive a renal transplant as early as possible in order to enhance their chances of long-term survival.