Niche Market, who finished fifth in the 2011 Grand National, is being retired by owner Graham Regan.
Regan announced on Wednesday that the 11-year-old would miss this year's National on 14 April with a leg injury.
But Regan has now opted to end the career of the 2009 Irish National winner, and told BBC Sport: "I am retiring the Niche.
"These are the downs in racing but he has given us some brilliant days out. Now it is up to us to look after him."
Niche Market, was rated at around 20-1 for this year's National, will be given to jockey Harry Skelton, who rode him to victory in the Irish National, and he will live at the stable of Harry's showjumping father Nick Skelton.
Regan said: "We will sort out his leg problem and I am then gifting him to Harry. He will live at Nick Skelton's stable where he will hopefully enjoy a long and deserved retirement."
The horse was second in a veterans' chase at Newbury on Saturday and runner-up in the Becher Chase over the National fences at Aintree in December.
Niche Market, who was pulled up in the 2010 Grand National after being struck into by another horse, had been allocated a weight of 10st 5lb for this year's race, 8lb less than when he finished fifth.
"We thought we had a cracking chance in the National," added Regan.
It means trainer Paul Nicholls will have Neptune Collonges as his sole representative in next month's Aintree showpiece.