The Three Chimneys Farm's homebred Guarana puts her undefeated record on the line for trainer Chad Brown against some deep opposition.
The daughter of 2004 Breeders' Cup Classic winner Ghostzapper has been a dynamo in her three starts.
She started by winning her debut at Keeneland in April by a massive 14.75 lengths, went to Belmont Park's Acorn Stakes in June to win by six lengths and then passing her two-turn test when she wired Saratoga's G1 Coaching Club American Oaks on July 19.
A Cotillion win would give Guarana a clear divisional lead over stablemate Dunbar Road who won Saratoga's G1 Alabama Stakes on August 17.
Her rivals include Serengeti Empress, who is taking another shot at Guarana after she set a torrid pace when a clear second in the Acorn.
Jose Ortiz chose to stay with Guarana while his brother Irad will climb aboard Serengeti Empress.
The daughter of Alteration won the G1 Kentucky Oaks at Churchill Downs in May for trainer Tom Amoss and was also a super second in Saratoga's G1 Test Stakes in August. She boasts a career record of five wins from 10 starts including wins in the G2 Pocahontas Stakes as a 2YO by 19.5 lengths and the G2 Rachel Alexandra in February.
Of the 11 entrants, seven are graded stakes winners this year.
Kaleem Shah's Bellafina will wear blinkers in the Cotillion after working with them at Santa Anita.
The Simon Callaghan-trainee was a dual G1 winner last year and took the G1 Santa Anita Oaks in March before a fifth in the Kentucky Oaks and third in the Test Stakes.
Bellafina will have Flavien Prat aboard.
Jaywalk will break from the outside under Joel Rosario, who was aboard when she crushed the G1 Breeders' Cup Juvenile Fillies by 5.5 lengths.
She finished third in the G1 Ashland earlier this year, was disqualified to 13th in the Kentucky Oaks and then rebounded to win the G3 Delaware Oaks by nine lengths.
The G3 Monmouth Oaks winner Horologist is riding a four-race win streak for trainer John Mazza. Luis Saez will ride the daughter of Gemologist, who has won half of her 10 starts.
After winning the G2 Davona Dale earlier this year at Gulfstream Park, Jeltrin was tenth in the Kentucky Oaks, third in the Acorn and third in the G1 Mother Goose before running fifth in the Test.
However over the Parx course the daughter of Tapizar rolled home to win the Cathryn Sophia by 7¾ lengths. Alexis Delgado owns and trains.
Street Band rounds out the top contenders. The Larry Jones trained filly won the G2 Fair Grounds Oaks and the G3 Indiana Oaks in July and was third in the G1 Alabama.
Saturday's $1 million Pennsylvania Derby will be missing divisional leader Maximum Security, leaving Triple Crown rivals War Of Will and Improbable to square off in a small but select field.
The morning line favorite Maximum Security was scratched early in the week due to an acute bout of colic.
Maximum Security, the G1 Florida Derby and G1 Haskell Invitational winner, was first home in the Kentucky Derby before being disqualified.
In his absence War of Will and Improbable, who met in both the Kentucky Derby and Preakness Stakes, are dominating what is now a six-horse field.
War Of Will was a troubled seventh in the Derby then went to a new level top win the G1 Preakness for trainer Mark Casse.
The son of War Front also won the G3 LeComte and G2 Risen Star Stakes at Fair Grounds this winter but has disappointed in his last two starts, running ninth in the G1 Belmont Stakes in June and fifth in Saratoga's Jim G2 Dandy on July 27.
WinStar Farm, China Horse Club International and Starlight Racing's Improbable was a winter book favorites for the Kentucky Derby and came in with strong form after running second in Oaklawn Park's G2 Rebel Stakes and the G1 Arkansas Derby (G1) but could manage only fourth for trainer Bob Baffert.
The son of City Zip then followed that up with a flat sixth as the favorite in the Preakness before bypassing the Belmont and returning to win at Del Mar on Augustr 25, his first win this year and taking his record for four wins in eight starts.
Drayden Van Dyke was aboard at el Mar but Mike Smith, who was on for the Preakness, is back for the Penn Derby. Improbable shipped in from Santa Anita on Wednesday.
Also in the field is Allied Racing Stable's Mr Money, who steps up a level from a quartet of lopsided G3 victories for trainer Bret Calhoun including the Indiana Derby.
His most recent victory was by six lengths in the West Virginia Derby at Mountaineer Park on August 3 with his run of four wins by a combined total of more than 20 lengths.
Spun To Run won the local prep, the G3 Smarty Jones early this month for trainer Juan Carlos Guerrero.
Meanwhile Code Of Honor, winner of the G1 Travers Stakes at Saratoga in August, will have his next start in the G1 Jockey Club Gold Cup at Belmont Park on September 28.
The Jockey Club Gold Cup is an automatic qualifier for the Breeders' Cup Classic, and remains a possible target for the son of Noble Mission.
Trained by Shug McGaughey, he also won Gulfstream Park's G2 Fountain of Youth in March and was a promoted second in the G1 Kentucky Derby before winning the G3 Dwyer Stakes at Belmont in July.
"The Breeders' Cup is still in consideration," McGaughey said. "We just have to get through this one and we'll see where we go from there."