Tina, who lived in Tennessee, was recognised in 2007 by the Guinness Book of Records as the world's tallest horse.
News of her death came as another Shire in Australia, called Noddy, was laying claim to the record.
Tina, who was owned by Jim and Marge Williams, had been taken to Auburn University in Alabama for what was understood to be surgery to correct a hip problem.
She appeared fine upon arrival but then went down and never got up again. She died 30 hours later, despite intensive veterinary care, which included intravenous feeding.
Tina stood 80 inches (2.03m) at the withers, a full inch taller than the previous tallest horse.
In Australia, three-year-old Noddy, weighing in at 1.3 tonnes, is reported to be an inch taller again.
Horsetalk hopes to bring you the story of Noddy in the next few days.