Big Buck's is out to make history with an unprecedented fourth straight win in Thursday's World Hurdle at Cheltenham.
The nine-year-old, trained by Paul Nicholls, is also bidding to equal the record of 16 consecutive wins over hurdles set by Sir Ken in the 1950s.
Chief danger is Oscar Whisky, third in last year's Champion Hurdle, running over three miles for the first time.
Thursday's other races include the Ryanair Chase, in which Alberta's Run seeks a hat-trick.
The Festival has been overshadowed this year by the deaths of five horses on the opening couple of days.
Big Buck's has not lost a race for more than three years since his defeat over fences in the 2008 Hennessy Gold Cup at Newbury when he unseated jockey Sam Thomas.
He has won more than £1m in prize money, his last victory having come in the Cleeve Hurdle at Cheltenham on Festival Trials Day in January.
The 2011 Welsh Champion Hurdle winner Oscar Whisky is two years his junior, has won his last three races and could potentially pose the biggest threat to his winning run.
Other contenders in the 13-strong field include Dynaste, trained by David Pipe, who came second, seven lengths behind Big Buck's, last time out.
Ireland's last winner of the World Hurdle was Doran's Pride in 1995 and Irish trainer Willie Mullins saddles last year's third Mourad.
Mullins also runs Grade One winner Thousand Stars, along with Mikael D'Haguenet and So Young, while mare Voler La Vedette represents Colm Murphy.
The Ryanair Chase (1440 GMT), which is run over two miles and five furlongs, boasts one of the most competitive fields of the four-day meeting.
Riverside Theatre, who is part-owned by actor Jimmy Nesbitt, missed last year's race with a fractured pelvis but made a winning return at Ascot in February.
Kalahari King, trained by Ferdy Murphy, has been placed at the last three Festivals, including when runner-up to Albertas Run in 2011.
Noble Prince, Somersby, Rubi Light and Medermit are among others in the line-up.
The card gets under way with the Jewson Novices' Chase (1330 GMT), in which last year's Champion Hurdle runner-up Peddlers Cross attempts to go one better over fences.
Peddlers Cross started his chasing career with two wins at Bangor before coming home second behind Sprinter Sacre at Kempton in December.
Pipe's Our Father and Festival specialist Buena Vista are leading contenders in the Pertemps Final (1405 GMT), while the Somerset trainer has Salut Flo in the Byrne Group Plate (1600).
Mullins has Up The Beat lined up for the Fulke Walywn Kim Muir Challenge Cup (1640), with last year's Irish Grand National third Sunnyhillboy representing Jonjo O'Neill.
Thursday's action concludes with the St Patrick's Derby, a charity flat race over a mile and five furlongs in aid of Cancer Research UK.
The 12 jockeys include three-day event rider Tina Cook and Joanne McCain, the sister of trainer Donald.
World Hurdle, Three miles, 1520 GMT, Thursday
1 111-111 BIG BUCK'S 9 11-10 Paul Nicholls Ruby Walsh
2 14-5452 CROSS KENNON 8 11-10 Jennie Candlish Alan O'Keefe
3 216-142 DYNASTE 6 11-10 David Pipe Tom Scudamore
4 6-02226 FIVE DREAM 8 11-10 Paul Nicholls Ryan Mahon
5 031112 MIKAEL D'HAGUENET 8 11-10 Willie Mullins IRE
6 242231 MOURAD 7 11-10 Willie Mullins IRE
7 31-F111 OSCAR WHISKY 7 11-10 Nicky Henderson Barry Geraghty
8 1310-12 SMAD PLACE 5 11-10 Alan King Robert Thornton
9 13-6111 SO YOUNG 6 11-10 Willie Mullins IRE
10 221123 THOUSAND STARS 8 11-10 Willie Mullins IRE
11 141112 VOLER LA VEDETTE 8 11-3 Colm Murphy Andrew Lynch IRE
Pinstickers' guide: While boringly obvious, it is difficult not to side with Big Buck's, albeit he might have a tougher task this time. Oscar Whisky and Thousand Stars are both solid.
Verdict: 1 Big Buck's 2 Oscar Whisky 3 Thousand Stars