"The patient who had two legs transplanted at the Hospital La Fe in 2011 had to undergo an operation to amputate the two extremities," said a statement issued by the hospital in Valencia, eastern Spain.
The patient, who contracted an unrelated illness, had the two limbs amputated about a year and a half after the milestone transplant, it said.
He had to stop taking immunosuppressant drugs required to prevent his body rejecting the transplant because the medicine was complicating the treatment of the illness, the hospital said.
The patient had not given permission for the release of information about his current treatment, the hospital added.
Renowned surgeon Pedro Cavadas led the team that carried out the original 10-hour transplant operation, which was completed on July 10, 2011.
The double leg surgery was touted as a world first.
More than 50 personnel were involved including surgeons, nurses, anaesthetists and transplant coordinators.
But the patient, a man in his 20s who has not been identified, was obliged to take immunosuppressant drugs for the rest of his life.
In an interview with the newspaper 20 minutos around eight months after the transplant, Cavadas said the patient was moving his legs in the swimming pool and the recovery was going "very well".
The man had had both legs amputated above the knee after a traffic accident.
The height of the amputation prevented him from using a prosthesis, meaning that he would have been consigned to a wheelchair with "zero" chance of walking again, the transplant surgeon said at the time.