In 2002, 1329 patients with functioning transplants were prospectively tested for HLA antibodies in the 13th International Histocompatibility Workshop. Four years after testing, deceased donor graft survival among 806 patients not having antibodies in 2002 was 81% compared to 58% for 158 patients with HLA antibodies (p < 0.0001) and 72% for 69 patients with MICA antibodies (p = 0.02). Hazard ratio (HR) using death-censored graft survival from multivariate analysis of HLA antibodies was 3.3 (p < 0.00001) and 2.04 for MICA (p = 0.01). In the 14th Workshop, at 1 year follow-up, survival for 1319 patients receiving deceased donor grafts and no HLA antibodies was 96% compared to 94% for 344 patients with HLA antibodies (p = 0.0004) and 83% survival for 33 patients with MICA (p = 0.0005). HR from multivariate analysis: HLA antibodies was 3.6 (p < 0.00001) and 6.1 for MICA (p = 0.006). Twelve patients with donor specific antibodies tested by single antigen beads had a 1 year survival of 64% (p = 0.008), and 27 patients with non-donor specific 'strong' antibodies had a 66% survival (p = 0.0003) compared to 92% survival in those with no antibodies. In conclusion, these two prospective trials, after 1 and 4 years, provided strong evidence that HLA and MICA antibodies are associated with graft failure.