Labour backbencher Marsha Singh is to step down as an MP, triggering a by-election in his Bradford West constituency.
The MP said his resignation was on medical advice owing to "serious health problems".
Mr Singh has represented Bradford West, a Labour stronghold, since 1997.
In a statement today, he said: "I have been suffering with serious health problems for some months now.
"I have had wonderful treatment from our fantastic NHS doctors and nurses here in Bradford. But it has become clear that it is going to take much longer than I'd expected to recover."
Labour leader Ed Miliband paid tribute to Mr Singh's "tireless work for the people of Bradford West".
"He is a man who entered politics for all the right reasons - to make a positive difference to people's lives and to stand up for social justice in the community where he grew up," Mr Miliband said.
"He will be missed greatly by his parliamentary colleagues.
"He is doing the right thing by listening to the doctors - his priority now has to be to concentrate on regaining his health - and I wish him all the best on his long road to recovery."
Labour MPs took to Twitter on Thursday morning to express their sadness that Singh would be leaving the Commons, including Barnsley MP Michael Dugher who said he had been "a great servant of Bradford".
Mr Singh, 57, was re-elected with a large majority of 18,401 in the 2010 general election.
Since 1997, he has been a member of the home affairs and international development select committees and was briefly a parliamentary aide to then Home Office minister Phil Woolas during the last Labour government.
Mr Singh said: "This is a sad day for me. I have been extremely proud to represent the people of Bradford West for the last 15 years.
"I'm passionate about Bradford. It is where I grew up and where my children were born, so it has been a great privilege to be asked by the electorate at four general elections to be their voice in Parliament.
"At this crucial time in our country, with David Cameron's Government making decisions that are hugely damaging for Bradford, people here deserve a Labour MP who can throw all their efforts into standing up for them.
"I would like to thank the people of Bradford West from the bottom of my heart for putting their faith in me, and for all the warmth and affection they have shown me.
"I would also like to thank the Labour Party for all the support they've given me, particularly over the last few months. And I would like to thank my family - I very much look forward to being able to focus on being a dedicated husband, dad and grandad."