St Nicholas Abbey, Aidan O'Brien's triple Coronation Cup hero, died on Tuesday morning, confirmed Coolmore.
The brilliant seven-year-old, winner of six races at the highest level, had to be put down after he suffered a bout of colic.
A statement issued by Coolmore read: "Regretfully St Nicholas Abbey has lost his brave battle after suffering a colic this morning.
"Surgery revealed a severe strangulating colon torsion that was unviable and he had to be euthanized on humane grounds."
The son of Montjeu faced a multitude of problems as he strived to recover from a fractured pastern he sustained last summer.
O'Brien's star had to be retired after suffering a leg injury on the gallops at Ballydoyle when being prepared for the King George VI And Queen Elizabeth Stakes.
Just two days after he underwent a major leg operation at Fethard Equine Hospital last July, St Nicholas Abbey had to have emergency surgery to be treated for colic.
He then had a further setback in August when it was discovered a steel weight-bearing pin in a cannon bone had broken, and then had a further serious blow in October with "mild laminitic changes in the left fore".
St Nicholas Abbey will be buried at Coolmore, who said: "This is extremely unfortunate as St Nicholas Abbey had been in terrific form, the laminitis was resolving very well and the fracture had healed better than expected.
"Coolmore would like to thank the surgeons, the international experts and all the staff at Fethard Equine Hospital who gave him such excellent care 24/7.
"We would also like to thank the multitude of well-wishers for all the cards and messages of support for St Nicholas Abbey.
"He will be buried in the graveyard here at Coolmore."