Background. After the introduction of cyclosporine A (CsA), 2-year graft survival of transplanted kidneys improved from less than 60% to more than 80%, but long-term graft survival and graft half-life have shown less change. This study investigates the impact of a range of demographic and treatment factors on long-term graft survival in renal recipients treated with CsA from all renal transplant centers in the United Kingdom. Methods. Data were obtained from the Long-Term Efficacy and Safety Surveillance study of renal transplant recipients receiving CsA (Neoral; Novartis, Basel, Switzerland). A total of 1,757 de novo patients with a functioning graft at I year were evaluated. The endpoints considered were the need for regular dialysis or death. A stepwise stratified Cox model was used to identify the factors associated with outcome. Results. Seven independent risk factors for allograft failure were identified: older recipient (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.2-2.6), male recipient (HR 1.8, 95% CI 1.2-2.7), younger donor (HR 1.7, 95% CI 1.2-2.5), above average creatinine (HR 1.9, 95% CI 1.3-2.8), chronic allograft nephropathy (HR 7.0, 95% CI 4.7-10.4), diabetic recipient (HR 2.2, 95% CI 1.2- 4.1), and neoplasm after transplant (HR 1.7, 95% CI 1.2-2.6). Conclusion. Seven independent risk factors were found to influence graft survival. Only two of these can be modified by clinical intervention, elevated serum creatinine at I year and the occurrence of chronic allograft nephropathy. To influence these two factors, the optimization of immunosuppressive therapy is essential.