John Wootton, 69, flew to Australia last year to donate bone marrow for his sick sibling Hazel McCaig, 66, who was suffering from acute leukaemia.
The Australian government was so impressed with his generosity they reimbursed his flight costs.
The operation appeared to have worked but Mr Wootton, of Wakefield, received an urgent phone call this week telling him his sister's leukaemia had returned and her only chance of survival was a second transplant.
Mr Wootton, who is getting ready to fly across the world again, said: "A week ago she went for a check-up and doctors found it had failed. It was such a shock, Hazel was saying she had never felt so well in years.
"They got in touch and asked me to get there as soon as possible.
"We have always been close, despite living at other ends of the world, so there is nothing I wouldn't do for my own sister."
Mr Wootton added: "We've also been told Hazel can only have this one more time – so the pressure is really on for it to work."
Doctors have told the mother-of-two that she could have just 12 months to live if the transplant fails. Mrs McCaig, a widow, who lives 150km north of Sydney, has already begun pre-transplant treatment.
Mr Wootton said: "Last time they took my bone marrow, froze it for three weeks and treated it before giving it to Hazel. This time once it is harvested it will be given straight to her, and the doctors think that this way it will have a better chance of being accepted."