Purpose To report our experience on third kidney transplantation, analyzing the complications and graft survival rates as compared to previous transplants. Methods Retrospective study of third renal transplants performed at our center. Outcomes were compared with a cohort of first and second transplants. Results Of a total of 4143, we performed 72 third transplants in 46 men and 26 women with an average age of 46 years and mean time on dialysis of 70 months. Thirty-seven patients were hypersensitized panel-reactive antibody (PRA) > 50%. They were all from deceased donors, with a mean cold ischemia time of 19.2 h. The extraperitoneal heterotopic approach was used in 88.8%, transplantectomy was performed in 80.6% and vascular anastomoses were realized mostly to external iliac vessels, using the common iliac artery in 15 cases, and the inferior vena cava in 16. The main ureteral reimplantation technique was the Politano-Leadbetter (76.4%). Third transplantation reported a significantly higher incidence of lymphocele (13.9% vs. 3.2% in first and 4.5% in second transplants; p  < 0.001), rejection (34.7% vs. 14.9% and 20.5%, p  < 0.001) and urinary obstruction (11.1% vs. 3.6% and 6.3%, p 0.002). Graft survival rates for first, second and third transplants were 87%, 86% and 78% at 1 year, 83%, 82% and 74% at 3 years and 80%, 79% and 65% at 5 years, respectively. Conclusion Iterative transplantation constitutes a valid therapeutic option with adequate surgical and survival results compared to previous transplants. It is a challenging procedure which must be performed by experienced surgeons.