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Trailing by 10-6 going into the closing 12 singles, Jose Maria Olazabal's men thrillingly won the first five matches out and went on to make sure of victory when Martin Kaymer downed Steve Stricker 1 up in the penultimate match.
He clinched it with a six-foot putt at the last, 21 years after his fellow German Bernard Langer missed from a similar distance to hand victory to the United States at Kiawah Island.
That gave the Europeans the 14 points they needed to make sure of keeping the small, golden trophy for another two years, and then minutes later Tiger Woods missed a four-footer at 18 against Francesco Molinari to hand overall victory to Europe 14 1/2 to 13 1/2.
"This is indescribable," Kaymer said.
"I was so nervous in the last two or three holes. Olazabal came up to me on the 16th and told me we needed my point to win the Ryder Cup. I loved that feeling. Loved it.
"You cannot compare the pressure of winning this to winning my major. I won that for myself. But today I could hear my team and hear all the people. My season hasn't been good but today I made a huge step for my confidence."
The Americans had started the 12 closing singles 10-6 ahead and needing just 4 1/2 points to win the cup for just the second time in the last decade, the other time being at Valhalla, Kentucky four years ago.
They got to that position by dominating the foursomes and fourballs play on Friday and Saturday, taking two sessions 3-1 and splitting the two others 2-2.
Jose Maria Olazabal's outgunned team were left with the mammoth task of winning eight out of the 12 singles to put the overall match score at 14-14, thus ensuring Europe retained the cup as holders.
No European side had ever managed to comeback from 6-10 down in the Ryder Cup and no US team had ever lost more than a two-point advantage on the final day since the competition began in 1927.
Olazabal loaded his top guns at the start of the singles slate and there was some early momentum as Luke Donald quickly went 2 up on Bubba Watson in the lead match and Europe eased ahead in three of the first five matchups with one all-square.
But gradually the US team settled in with some strong middle-order players and it became increasingly clear how huge the task on hand was for the Europeans.
Crucially though the first point home was a blue one as Donald led from start to finish to see off crowd-pleaser Watson 2 and 1.
The Englishman was four up with five to play, but missed a four-footer to win on the 14th. Watson took the 15th and then chipped in to nick the 16th before Donald clinched it with a superb bunker shot at 17.
Then Paul Lawrie, Europe's oldest player at 43, pulled off an upset by trouncing Tour Championship winner Brandt Snedeker 5 and 3.
And when world No 1 Rory McIlroy, who nearly missed his tee-time due to a mixup over time zones, completed a 2&1 win over the previously unbeaten Keegan Bradley, and Ian Poulter finished a perfect 4-0 by defeating Webb Simpson 2-up, the overall match was tied at 10-10.
Dustin Johnson beat Nicolas Colsaerts 3&2 to put the Americans back ahead only for Justin Rose to win the last two holes with monster putts to defeat Phil Mickelson 1-up.
Zach Johnson edged Graeme McDowell 2&1, but Sergio Garcia won the last two holes to stun Jim Furyk and Lee Westwood completed a 3&2 win over Matt Kuchar to make it Europe 13 United States 12.
Jason Dufner defeated Peter Hanson 2-up and it was level at 13-13.
It all came down to the last two matches and they were both all square at that point.
Woods moved one up on Molinari, but Kaymer took the 17th against Steve Stricker and he sunk the nerve-jangling six footer at the last to ensure Europe had the 14 points they needed.
By the time Woods flopped at the last, Europe had taken the singles by an unthinkable 8 1/2 to 3 1/2.
An emotional Olazabal paid tribute to the late Severiano Ballesteros, his great friend and Ryder Cup playing partner, who died from a brain tumour last year.
"Seve will always be present with this team," he said.
"He was a big factor for this event, for the European side, and last night when we were having that meeting, I think the boys understood that believing was the most important thing, and I think they did."
US skipper Davis Love said that he would not have done anything different in his tactics or selections.
"They played great," he said. "We had a couple of matches that got flipped there at the end that made it a little bit easier on them. This is a great team and we had a great week."
Collated final scores after Sunday's singles in the 39th Ryder Cup between the United States and Europe at Medinah Country Club outside Chicago:
Overall Score: United States 13 1/2 Europe 14 1/2
Singles
Bubba Watson (USA) lost to Luke Donald (Europe) 2 and 1
Brandt Snedeker (USA) lost to Paul Lawrie (Europe) 5 and 3
Keegan Bradley (USA) lost to Rory McIlroy (Europe) 2 and 1
Webb Simpson (USA) lost to Ian Poulter (Europe) 2-up
Dustin Johnson (USA) bt Nicolas Colsaerts (Europe) 3 and 2
Phil Mickelson (USA) lost to Justin Rose (Europe) 1-up
Zach Johnson (USA) bt Graeme McDowell (Europe) 2 and 1
Matt Kuchar (USA) lost to Lee Westwood (Europe) 3 and 2
Jim Furyk (USA) lost to Sergio Garcia (Europe) 1-up
Jason Dufner (USA) bt Peter Hanson (Europe) 2-up
Steve Stricker (USA) lost to Martin Kaymer (Europe) 1-up
Tiger Woods (USA) v Francesco Molinari (Europe) halved
Score: United State 3 1/2 Europe 8 1/2
Friday
Fourballs
Bubba Watson/Webb Simpson (USA) bt Justin Rose/Francesco Molinari (Europe) 5 and 4
Dustin Johnson/Matt Kuchar (USA) bt Nicolas Colsaerts/Paul Lawrie (Europe) 1-up
Sergio Garcia/Luke Donald (Europe) bt Tiger Woods/Steve Stricker (USA) 1-up
Rory McIlroy/Ian Poulter (Europe) bt Jason Dufner/Zach Johnson (USA) 1-up
Score: United States 2 Europe 2
Foursomes
Keegan Bradley/Phil Mickelson (USA) bt Lee Westwood/Luke Donald (Europe) 7 and 6
Justin Rose/Ian Poulter (Europe) bt Webb Simpson/Bubba Watson (USA) 1-up
Jason Dufner/Zach Johnson (USA) bt Nicolas Colsaerts/Sergio Garcia (Europe) 2 and 1
Jim Furyk/Brandt Snedeker (USA) bt Rory McIlroy/Graeme McDowell (Europe) 1-up
Score: United States 3 Europe 1
Friday
Fourballs
Bubba Watson/Webb Simpson (USA) bt Paul Lawrie/Peter Hanson (Europe) 5 and 4
Keegan Bradley/Phil Mickelson (USA) bt Rory McIlroy/Graeme McDowell (Europe) 2 and 1
Dustin Johnson/Matt Kuchar (USA) bt Justin Rose/Martin Kaymer (Europe) 3 and 2
Tiger Woods/Steve Stricker (USA) lost to Nicolas Colsaerts/Lee Westwood (Europe) by one hole
Score: United States 3 Europe 1
Foursomes
Phil Mickelson/Keegan Bradley (USA) bt Luke Donald/Sergio Garcia (Europe) 4 and 3
Jim Furyk/Brandt Snedeker (USA) lost to Rory McIlroy/Graeme McDowell (Europe) by 1 hole.
Jason Dufner/Zach Johnson (USA) bt Lee Westwood/Francesco Molinari (Europe) 3 and 2
Steve Stricker/Tiger Woods (USA) lost to Ian Poulter/Justin Rose (Europe) 2 and 1
Score: United States 2 Europe 2
