Multiple organ transplantations are used to treat chronic multiple organ failure. However, long-term mortality and graft tolerance remain to be evaluated. We carried out a retrospective and comparative analysis of 45 patients who underwent a combined liver and kidney (LK) transplantation (LKT) from the same donor. They were compared to 86 matched patients who underwent kidney (K) transplantation (KT). All patients had an organic renal failure associated with cirrhosis (n = 35) or with inherited disease (n = 10). Nineteen (42.9%) had been transplanted previously. The patients' survival rate was 85% at 1 year and 82% at 3 years. Seven patients died within the first 3 months, due to severe polymicrobial infection. Two patients in the LK population (4.2%) developed acute rejection of the kidney graft compared to 24 of the 86 matched renal transplanted patients (32.6%). In parallel, acute liver rejection was observed in 14 cases (31.1%) in the LK population. The occurrence of acute rejection was not associated with panel-reactive lymphocytotoxic antibodies (n = 16), nor with positive cross-matches (n = 3). Four of the 45 patients (8.8%) subsequently developed chronic renal allograft rejection, and 16 cases of chronic hepatic dysfunction were noted (42.2%). In conclusion, the overall survival rate following combined liver kidney transplantation is acceptable, and LKT can be proposed to patients with kidney failure associated with liver dysfunction, primary oxaluria or amyloid neuropathy. The main cause of mortality in this population was severe infectious complications. The frequency of acute kidney rejection was lower than in single transplantation.