Kim Bailey's charge was unfancied at 14-1 last year, but floored 11-8 favourite Politologue by seven lengths after being prominent throughout in the Grade One feature.
Having made a successful reappearance in the Peterborough Chase at Huntingdon four weeks ago, First Flow will attempt to win the prestigious Ascot prize a second time.
But he is likely to face a stiffer task this time, with Nicky Henderson's Shishkin and the Willie Mullins-trained Energumene among the entries. Both are unbeaten over fences and have been successful at the top level.
"I'm absolutely delighted with him and he's on course to take on Shishkin, and anyone else, who wants to turn up, at Ascot," said Bailey.
"It will be a bit tougher, but then he was an unfancied horse in the race last year."