Story highlights Paul Ryan's signature policy agenda, called "A Better Way," failed Friday with a vote on health care

"We came really close today, but we came up short," the House Speaker said at a news conference

Washington (CNN) House Speaker Paul Ryan conceded the biggest defeat of his political career Friday: Republicans have failed to repeal and replace Obamacare.

And after nearly three full months into the year, he now has to face a head-on a challenge that is likely to haunt his tenure as speaker for the foreseeable future: seemingly irreconcilable differences among his fellow Republicans.

"Moving from an opposition party to a governing party comes with growing pains," Ryan told reporters Friday. "And well, we're feeling those growing pains today."

The stunning setback was particularly excruciating for the 47-year-old, who made his name in Washington as a conservative policy wonk committed to repealing the Affordable Care Act and ascended to the powerful position of House speaker in fall 2015.

The bill that too many of his fellow colleagues ultimately rejected was based on Ryan's signature policy agenda, called "A Better Way."

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