Masters champion Bubba Watson hopes to add Muirfield to the list of courses where the left-handers' hoodoo has been broken.
Canadian Mike Weir ended a 40-year wait for a lefty major champion when he triumphed at the 2003 Masters.
His victory included, there have been six victories by left-handers at Augusta in the last 12 years – two of which were registered by Watson himself.
The 35-year-old arrives at Muirfield Village for Jack Nicklaus' Memorial Tournament knowing his best finish on the course is tied-23rd in 2007 and 2009.
But Watson is not willing to accept he cannot win around the Ohio venue, even if a left-hander has not succeeded there for 38 years.
"I don't think I've ever played very well here but I love coming back and challenging myself," he said.
"Hopefully now that I'm playing a little bit better, making my way a little bit better, hopefully it will show Sunday afternoon.
"It's just like Augusta. Remember, there wasn't very many lefties winning Augusta and then, now there's a few more lefties.
"Golf just goes in cycles. It's always up in the air but obviously with more righties in the field it makes it a little bit easier for righties."
Of more significance may be the impending US Open at Pinehurst in a fortnight's time but Watson insists that is not the focus this week.
"Truthfully, none of us here are thinking about the Open. We're all thinking about trying to win here," he told a press conference.
"None of us are trying to practise for that. We'd like to all shake the hand of Jack Nicklaus Sunday afternoon."
The headline group for the first two rounds of the Memorial sees world number one Adam Scott and Rory McIlroy, both winners either side of the Atlantic on Sunday, together with Australian Jason Day.
American Matt Kuchar, who tees off with US Open champion Justin Rose and Steve Stricker, knows defending the title he won last year will not be easy.
"I've had great success in the past and feel the state of my game is still pretty good" - Matt Kuchar on defending his title
"Only a few guys have a whole lot of opportunities to defend," he said.
"Winning a golf tournament is difficult to do. You don't win that many so to try to defend, of course, is hard.
"I feel excited and optimistic about my chances. This course has been really good to me, one of my favourite places to come.
"I've had great success in the past and feel the state of my game is still pretty good."
Nicklaus revealed the injured Tiger Woods, winner of this tournament on five occasions who had back surgery on 31 March, had called to say sorry for not being able to play.
"He was saying that he felt bad about not being able to be here," said the 18-time major winner.
"He said he's doing well, progressing well, and he's looking forward to getting back into the game. He misses it."
Nicklaus' major haul remains Woods' sole target and the 74-year-old has not written him off winning the five he needs to break the record just yet.
"His biggest stumbling block probably is going to be his health, and I think his health is something that he thinks he's doing very well with," Nicklaus added.
"If he's healthy, Tiger's got 10-plus years to play top-quality tournament golf."