Taking a different approach from the Senate, where Democrats on Thursday paved the way for the nuclear deal to move forward by scuttling a disapproval resolution, the House instead voted on a resolution to approve the agreement.
The resolution failed 162-269, with not a single Republican voting in favour and 25 Democrats joining them.
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"As we conclude the most consequential national security debate since the decision to invade Iraq, I am gratified that the lawmakers, led by Democratic Leader Pelosi, who have taken care to judge the deal on the merits are joining our allies and partners around the world in taking steps that will allow for the implementation of this long-term, comprehensive deal," Obama said.
"Now, we must turn to the critical work of implementing and verifying this deal so that Iran cannot pursue a nuclear weapon. In doing so, we'll write the latest chapter of American leadership in the pursuit of a safer, more hopeful world," the US President said.
The vote will not prevent the nuclear agreement from taking effect with the Senate having failed to advance a disapproval resolution.
The Republican party is opposed to the Iranian nuclear deal, which took several years by the US and its allies to negotiate with Iran.
"This deal is deeply flawed. It makes the world less safe," Congressman Ed Royce, Chairman of the House Foreign Affairs Committee, said.
"President Obama says there are no other options and that if we don't accept his deal, then we will go to war. What utter nonsense. The president has negotiated a ticking time bomb that will result in war, not prevent it," Congressman Paul Gosar said.
"To make matters worse, President Obama broke the law by not transmitting the 'side agreements' to Congress and the awful negotiating skills of this administration have put our children and nation at risk," he alleged.
Congressman Mike Kelly said, "Do not sacrifice the safety, the security and the stability of 300 million Americans for the legacy of one man."
"The president ought to release to the American people the details of these secret side agreements right now or withdraw this entire proposal," said House Majority Whip Steve Scalise.
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