The Kentucky Derby is a Grade I stakes race for three-year-old Thoroughbreds at a distance of 1+1⁄4 miles (2.0 km) and has been run at Churchill Downs racetrack since its inception in 1875.

After the 2020 Derby had been postponed to September because of the COVID-19 pandemic and held behind closed doors, the 2021 edition returned to its traditional May schedule and allowed spectators, although in reduced numbers and with social distancing measures in place.

[10][a] The field is limited to twenty horses who qualify based on points earned in the 2021 Road to the Kentucky Derby, a series of designated races that was first introduced in 2013.

The first four of these major preps were run in late March 2021 and were won by Hot Rod Charlie, Like The King, Rebel's Romance, and Known Agenda respectively.

[12] The favorite for the 2021 Kentucky Derby was Essential Quality, who was undefeated in all five of his previous starts including the Breeders' Cup Juvenile and Blue Grass Stakes.

The Derby typically has one of the highest audiences of all North American sporting events, in the range of 150,000 in recent years, which includes a large infield crowd.

For the Derby, jockey John Velazquez decided to change tactics and instead sent Medina Spirit to the early lead with Soup and Sandwich in second.

In a close finish, Medina Spirit held off his rivals to win by half a length over Mandaloun with Hot Rod Charlie just edging Essential Quality for third.

Baffert claimed that Otomax was used to treat dermatitis on the horse's hind end, and that he did not realize the ointment had betamethasone until after the positive test was reported.

Baffert said he never attempted to "game the system or get an unfair advantage", and quoted pharmacologists who told him that "21 picograms of betamethasone would have no effect on the outcome of the race.

Bill Carstanjen stated for Churchill Downs that "given these repeated failures over the last year, including the increasingly extraordinary explanations, we firmly believe that asserting our rights to impose these measures is our duty and responsibility.

[25][26] At the time of his death, Medina Spirit was still an active racehorse, even recently winning the October 2021 Awesome Again Stakes and then afterwards finishing second in the November 2021 Breeder's Cup Classic.

[27][28] Three days before the horse's death, Baffert's attorney Craig Robinson publicly acknowledged that the kind of betamethasone which Medina Spirit was injected with was banned by Kentucky state rules, while also alleging it was used to improve his skin condition rather than enhance performance.

Ky federal judge Claria Horn Boom dismissed the class action filed by thirty plaintiffs led by Michael Beychok.

Earlier, the United States Court of Appeals for the Sixth Circuit also dismissed similar bettors' lawsuit led by Anthony Mattera on May.