Irishman Harrington accepted an invitation to compete at Port Royal Golf Course in Southampton after Open champion Ernie Els withdrew on Saturday with an ankle injury.
"Hopefully this is third time a charm," triple Major winner Harrington said while preparing for Tuesday's opening round in the 36-hole event.
"I've come close twice in Grand Slams and hopefully it will be that close coming down the stretch this week and it would fall in my favour."
Harrington lost to Argentina's Angel Cabrera in a play-off for the 2007 title and was edged out by American Jim Furyk in 2008 at the event which traditionally brings together the winners of the year's four Majors.
"It's funny, I can't remember the play-off which I obviously lost to Jim Furyk, but I really remember the one I lost to Cabrera," Harrington said.
"He got the last (hole) to get into the play-off. I thought I had it won. I remember that one all right."
Before getting his late call-up for Bermuda, Harrington had initially planned to compete in this week's European Tour event, the BMW Masters at Lake Malaren Golf Club in Shanghai.
"I was due to travel to China on Sunday night," Harrington said. "So on Friday, I was practising and my manager rang me and said there's a possibility that Ernie may pull out and would I be interested. I said yeah, I'd be interested.
"The word came on Saturday afternoon, late Saturday afternoon, that Ernie had pulled out. As unfortunate as it is for Ernie ... it was good news for me."
Harrington accepted his invitation after the second and third alternates, Graeme McDowell and Tiger Woods, both said they were unavailable.
The Irishman will be competing against Americans Bubba Watson, who won this year's Masters, Webb Simpson (US Open) and defending champion Keegan Bradley over the next two days.
Bradley, winner of last year's US PGA Championship, gained his spot in the field as the first alternate after Northern Ireland's Rory McIlroy pulled out due to a scheduling conflict.
McIlroy, who clinched his second Major title by a staggering eight shots at this year's US PGA Championship, had already committed to the BMW Masters in China.
Left-hander Watson was delighted to be in Bermuda, having book his place in the field by landing his first Major victory at Augusta National in April.
"Coming over here is where it really hit home that I won a Major," he said. "I get to play in this, and there's only four guys.
"It's pretty special to be here and be a part of this. Hopefully I can do it again one day so I can come back."
The Grand Slam of Golf, billed as "the most exclusive tournament in golf", was held in Hawaii from 1991 to 2006 before moving to Bermuda in 2007.
- Sports & Recreation
- Port Royal Golf Course
- Ernie Els