Vino Rosso has won the $6 million Classic at the Breeders' Cup by 4-1/4 lengths, upsetting 5-2 favourite McKinzie in a race marred by a serious injury to one of the runners.

Mongolian Groom was pulled up in the straight as the rest of the field charged to the finish line.

Santa Anita has been the site of 36 horse deaths since December. Track owner The Stronach Group rushed to implement changes to rules involving medication and training.

The Breeders' Cup also beefed up its own pre-race exams and observations of Cup runners with the gelding's injury the only one in the 14 races over the two-day meeting.

A green screen was rushed onto the track to block Mongolian Groom from the view of 67,811 fans and a prime-time television audience.

He was loaded onto an equine ambulance and taken to a hospital beside the course.

"We know he's injured his left hind leg," veterinarian Dr Al Ruggles said.

Another on-call vet described the injury as "serious".

Bred in Kentucky by Calumet Farm, Mongolian Groom is trained by Ganbat Enebish and owned by Mongolian Stable.

Winning co-owner Mike Repole called Mongolian Groom's injury "the worst part of this game".

"For us, horse safety is very, very important. Prayers for the horse. Prayers for the connections of the horse. It's got to be really, really tough. It's very sad," Repole said.

Winning trainer Todd Pletcher said he was concerned about horse safety at Santa Anita coming into the season-ending world championships.

"We were anxious, not only for running in huge races like this, but hoping everything would go smoothly and safely," he said.

"Everyone took every precautionary measure they possibly could."

Vino Rosso went off at 9-2 for Pletcher, who won his first Classic.

"It's one thing that was missing," Pletcher said. "It feels great."

Jockey Irad Ortiz jr earned a leading fourth Cup victory of the weekend.

The Bob Baffert-trained McKinzie, the 5-2 favourite, finished second with Higher Power third.