Mickelson holds the U.S. Open record with six runner-up finishes, and it's the only major keeping him from the career Grand Slam.
Mickelson had been holding out hope that with the potential of storms over Wisconsin, there might be a long enough delay that he could still make his tee time.
Injuries, graduations, a newborn and a new course have all been part of the 117th U.S. Open buildup but on Thursday the spotlight will be back on the leaderboard and the year's second major.
But when the year's second major championship got under way in ideal conditions on Thursday, Mickelson officially withdrew and left first alternate Roberto Diaz to take his place alongside Stewart Cink and Steve Stricker in a group due to tee off at 2.20pm local time. Yet the first alternate, Roberto Diaz, has been practising here for the past three days unsure whether he will play or not.
"Obviously it's a tournament that I want to win the most, and the only way to win is if you play", Mickelson said recently at the Memorial Tournament.
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As the pro golfer prepares to defend his championship title, he reflected on the past year by sharing another Instagram photo holding his U.S Open trophy.
"But this (the graduation) is one of those moments where you look back on life and you just don't want to miss it". Mickelson's wife, Amy, was due with her as the tournament opened.
"I'm not going to really be prepared for Erin Hills", Mickelson admitted.
PGA Tour Commissioner Jay Monahan says that golf has surpassed basketball and football in terms of participation, citing National Golf Foundation data. Mickelson attended that ceremony, too, though this was on a Wednesday.
But world number one Dustin Johnson endured a torrid start to the defence of his title with a double-bogey and two bogeys on the front nine.
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