Although acute rejection rates have fallen over time, how this relates to graft outcomes is not known. Using data from the ANZDATA Registry, we examined associations of rejection within six months of transplantation with graft and patient outcomes among kidney-only transplants performed between April 1997 and December 2004 in Australia and New Zealand. Associations of biopsy histology with outcomes of the rejection episode were also examined. Outcomes were examined among 4325 grafts with 1961 rejection episodes in total. Crude rejection rates have fallen by one-third over that time, but rates of graft survival are constant. The occurrence of acute rejection was associated with an increased risk of graft loss after 6 months (HR, adjusted for donor and recipient characteristics, 1.69 [1.36-2.11], p<0.001). Late rejection (first rejection >or=90 days) was associated with higher risk of graft loss (adjusted HR 2.46 [1.70-3.56], p<0.001). Vascular rejection was also associated with a higher risk of graft loss 2.07 [95% CI 1.60-2.68], p<0.001. The occurrence of acute rejection is associated with an ongoing increased risk of graft loss, particularly if that episode occurred late or included vascular rejection. The reduced rates of rejection have not been associated with improved graft survival.