BACKGROUND.: The shortage of organ donors presents a major obstacle for adequate treatment of patients with end-stage renal disease. Donation after cardiac death (DCD) has been shown to increase the number of kidneys available for transplantation. The present article reports on the first 25 years of our experience with DCD kidney transplantation. METHODS.: This observational cohort study included all DCD kidney transplantations recovered in our procurement area from January 1, 1981 until December 31, 2005 (n=297). Patients were followed up until the earliest of death or December 31, 2006. Clinical outcomes were compared with matched kidney transplantations from brain dead donors (DBD, n=594), using multivariable regression models to adjust for potential confounders. RESULTS.: DCD activity resulted in a 44% increase in the number of deceased donor kidneys from our organ procurement area. After adjustment for potential confounders, the odds of primary nonfunction and delayed graft function were 7.5 (95% CI, 4.0-14.1; P<0.001) and 10.3 (95% CI, 6.7-15.9; P<0.001) times greater, respectively, for DCD kidneys compared with DBD kidneys. The high incidence of primary nonfunction of DCD kidneys resulted in an increased rate of graft loss (HR, 1.82; 95% CI, 1.37-2.42; P<0.001). However, DCD kidneys that did not experience primary nonfunction functioned as long as DBD kidneys (HR, 1.05; 95% CI, 0.73-1.51; P=0.79). Patient survival of DCD and DBD kidney recipients was equivalent (HR, 1.16; 95% CI, 0.87-1.54; P=0.32). CONCLUSIONS.: The benefits of DCD kidney transplantation outweigh the increased risk of early graft loss. Expansion of the supply of DCD kidneys is likely to improve the treatment of wait-listed dialysis patients.