Four years after celebrating his first Kentucky Derby triumph, trainer Doug O'Neill is in prime position to toast another with favourite Nyquist.

In 2012, Mario Gutierrez piloted the O'Neill-trained I'll Have Another to Derby glory and the same jockey will be aboard on Saturday (Sunday AEST) when the unbeaten Nyquist starts from gate 13 of 20 at Churchill Downs.

"It has allowed me to not be overwhelmed this time," O'Neill said.

"We found out that time that we had success doing what we'd been doing all along. It worked.

"So we're just doing that again - same patterns, same style. We just want to stay on course. That's what's going to work. We know that now."

Nyquist, who has won seven times at four different tracks, was rated the 3-1 early favourite and his connections were delighted with his barrier draw.

He started from the same alley when he won the Breeders' Cup Juvenile in October.

"It's good, lucky 13," Nyquist's owner, Canadian businessman J Paul Reddam, said.

"It's been our lucky number."

Second choice in the first leg of US racing's Triple Crown is Exaggerator, an 8-1 shot with Creator, Gun Runner and Mohaymen joint third picks at 10-1.

The strategy for the 1-1/4 mile (2000m) race could change markedly after Danzing Candy, winner of the San Felipe at Santa Anita, was drawn in 20.

Danzing Candy and Outwork, who will start from 15, were widely considered to be the likely pacesetters.

O'Neill had been hoping Nyquist would start outside Danzing Candy and Outwork so jockey Gutierrez could closely monitor the early going, but he may now want Nyquist to set the pace.

"I wouldn't mind that at all," O'Neill said.

"I think Nyquist has shown the versatility to win on the lead and from off the pace, so we've got options, I think."