Second renal transplants are historically associated with a poor prognosis. The aim of the present study was to assess long-term survival of second renal grafts from deceased donors performed at our center and to analyze risk factors associated with long-term graft outcome. Sixty-five second renal grafts were enrolled into this study, and compared to primary ones performed during the same period. Kaplan-Meier curve showed a graft survival rate of 89.2% at 1 year, 80% at 3 years, and 63.1% at 5 years, which were similar to that of primary graft. Univariate analysis showed that time to first graft loss, cold ischaemia time, HLA mismatch, primary maintenance immunosuppressant, acute rejection episodes, and serum creatinine at 1 year were significantly associated with regraft survival. Cox regression demonstrated the dominant effect of acute rejection episodes, primary maintenance immunosuppressant, serum creatinine at 1 year, and time to first graft loss as predictor of second graft outcome. However, when long-term survival of second graft was examined on the basis of Kaplan-Meier estimates, HLA mismatch was found to be significant. The second graft had more benefits of improved pre-transplant screening and post-transplant management, and its survival rate was satisfactory and similar to that of primary one. Immunologic factors such as acute rejection and primary immunosuppressant are the main determinants of long-term renal transplantation outcome.