Hoffman carded six-under-par 66 to head an worldwide leaderboard after the second round at Bay Hill in Orlando, one stroke ahead of Argentine Emiliano Grillo and two in front of Englishman Matthew Fitzpatrick.
The two Americans have a three-shot lead over Englishmen Tyrrell Hatton and Matthew Fitzpatrick, and Australian Marc Leishman.
He then saved par from the back bunker on the par-3 17th hole, sinking an seven-foot to maintain his one-shot lead over Kisner and Hoffman, the 54-hole co-leaders.
Kisner could have been in the lead all by himself, but he bogeyed No. 18, a hole he probably wants back.
"I knew I needed a good finish to run down Kisner", he told the PGA Tour Web site after turning his fortunes around with birdies at the final three holes.
Ketel One Vodka has launched a Limited Edition Collector's Item Arnold Palmer bottle on Thursday. "Week in and week out you're trying to win, but to be in position at Arnie's event is a special spot".
Perhaps that is understandable, as this tournament marks only the third event of the year for the four-time Major champion.
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Before he left, he was one of the League's best shot-blockers, averaging 1.8 blocks per game throughout his career. He announced in January that he was "stepping back into the game" adding "I really missed the game".
He decided instead to play Bay Hill for the fourth time in the last 10 years.
McIlroy and Palmer had dinner that week - the King insisted McIlroy have Bay Hill's famous banana split - and the connection was immediate.
Rickie Fowler also made the most of the morning conditions and matched McIlroy's 65 to also move into contention going into Sunday's final round.
"If I did win I sure wish he was here to have a drink with him afterwards, that's for sure", Kisner said of Palmer. He then made one birdie and eight pars on the back nine.
"It was unbelievable for him to open up to a struggling Tour pro like me", Snedeker said this week, according to Golf.Com.
Fowler, the world number nine, picked up four more strokes - while also saving his par from the water at 11, pants rolled up to the knees - and then landing an Eagle put on the par-five 16th. He was just shy of a 59, missing a 9-foot putt on No. 18, but he won't need to post a number quite so impressive to take home the title this week.
Fowler started his day at 2-over for the tournament, 12 shots behind the leader and McIlroy was at 1-over and 11 behind but after both shot red-hot 7-unders at Bay Hill, they were the two biggest names on the board by nightfall.