There is not enough information regarding risk factors for renal graft loss in Mexico and Latin America. The aim of this study was to analyze risk factors associated with graft loss in our renal transplant (RT) population. Clinical records of 326 patients with a first RT performed between August/76 and June/99 were reviewed. Clinical and laboratory variables were recorded, as well as the final patient and renal function status. Survival analysis by Kaplan-Meier method; mortality risk by multivariate Cox's proportional hazard model. At the end of the study, 275 patients were alive, 30 were dead, 21 lost to follow-up; 65 patients (20%) had reinitiated dialysis. Patient survival at 1, 3, 5, 8, and 10 years was 92%, 86%, 81%, 77%, and 77%, respectively. Graft survival at 1, 3, 5, 8, and 10 years was 87%, 73%, 64%, 50%, and 47%, respectively. In the univariate analysis, the following were significantly associated (p < 0.05) with graft loss: acute rejection episodes, cadaveric donors, and HLA haplotype mismatches. In the multivariate analysis, only acute rejection (RR 2.12, p = 0.002) and a lower HLA haplotype matching (RR 0.37, p = 0.002) predicted graft loss. In Mexican population, graft survival was similar to the reported in developed countries. The main risk factors for long-term graft failure were acute rejection and HLA haplotype mismatching.