David Miliband told ITV News "I am leaving politics" as he steps down as an MP to take on a charity role based in New York.
He admitted life had been tough since losing the leadership election to his brother Ed.
Political Editor Tom Bradby began by asking him whether the move means an end to his political career:
The former Foreign Secretary David Miliband has told ITV News: "I am leaving politics."
He told political editor Tom Bradby it is "not fair for me to spend my time looking backwards and inwards" about losing the Labour leadership election to his brother Ed.
He denied any falling out with his brother: "We fought a leadership election but we don't fight each other, Ed and I. That's not the Miliband way."
But he admitted: "Is it tough? Of course it's tough."
He said he "kept him [Ed] informed" about his new role.
David Miliband's local Labour party has said they want to choose their own MP, something he said they have not done in living memory.
John Anglin, secretary for the Constituency Labour Party in South Shields, said: "We are very surprised and it's a great loss to the Labour Party but that is what he has decided to do.
"He's done a lot of good work up here, with schools especially, but he's got a family and he knows what he wants to do.
"We wish him all the best but now we have to concentrate on South Shields and make sure we get a good MP.
"We want to make sure we are allowed to choose our own MP, something we have not done in living memory.
"We have a Labour-run council, which is doing great work, and we have the people up here who are capable of becoming an MP."
Bill Clinton has congratulated David Miliband on his appointment with the International Rescue Committee.
He said: "I congratulate the IRC on the appointment of David Miliband as its president. I have known David almost twenty years. He is one of the ablest, most creative public servants of our time."
Ed Miliband has said the "door was open" for his brother David to return to front line politics but he has taken the decision to take on a new role based in New York. The Labour leader said his brother will be "serving the world" with his new charity position:
Former Prime Minister Tony Blair has paid tribute to David Miliband, following news of his resignation as an MP.
"I congratulate David on his appointment to a major international position. It shows the huge regard in which David is held worldwide. I'm sure he will do a great job. He is obviously a massive loss to UK politics.
"He was the head of my policy unit and then a truly distinguished Minister in the Government and remains one of the most capable progressive thinkers and leaders globally. I hope and believe this is time out not time over."
Labour Leader Ed Miliband has said he is "delighted" for his brother David, who has announced he will be stepping down as MP to take a new role at a charity based in New York.
In a statement he said: "Having spoken to him a lot over the past few months, I know how long and hard he thought about this before deciding to take up the offer. I also know how enthusiastic he is about the potential this job provides...
"As for us, we went through a difficult leadership contest but time has helped to heal that. I will miss him. But although he is moving to America, I know he will always be there to offer support and advice when I need it.
"British politics will be a poorer place without David. But his huge talents will be serving people around the world. I hope and believe that at some point in the future he can once again make a contribution to British public life."
David Miliband has published his letter of resignation on his website. In it he says that following the leadership election - in which he lost out to brother Ed - he said he took a role on the "frontline" in order to give his brother space and the ability to lead "without distraction".
He said: "As you know, I see every day the damage this shocking government is doing to our country, and passionately want to see Labour back in power.
"After the leadership election, I felt I could be most helpful to the party on the front line, in South Shields and around the country, rather than on the front bench in Parliament.
"I felt this gave Ed the space and at the same time the support he needed to lead the party without distraction. He has done so with real success, leading a united team that has taken the fight to the Tories.
"I am very pleased and proud that our shared goal of making this a one-term government is achievable."
Labour MP David Miliband has stepped down as MP to become the president and CEO of the International Rescue Committee in New York. He has tweeted his letter of resignation to Alan Donnelly, chair of the South Shields Constituency Labour Party: