The California congresswoman also accused the GOP of not sharing a belief that "health care is a right" for all Americans.
Pelosi said individual health plan premiums and deductibles could increase dramatically, by 35 percent to 40 percent above current levels, if the Republicans did two things to "sabotage" Obamacare.
One would be killing the ACA mandate that most Americans have insurance or pay a fine. The second would be if GOP lawmakers refuse to continue funding subsidies to insurers that lower out-of-pocket costs for millions of Americans.
Either move, warned Pelosi, would be "totally irresponsible."
"But they want it to be a self-fulfilling prophecy," she said.
Pelosi was referring to the fact that President Donald Trump and Republicans in Congress have repeatedly claimed that Obamacare is a failure and causing Americans harm.
Pelosi and other Democrats strongly dispute that claim, and say the ACA needs to be improved, not gutted.
Ryan, R-Wis., said Wednesday that Obamacare will cause a "collapse" of the American health-care system.
He pointed to double-digit percentage increases in premiums, insurance plans exiting the marketplace and the fact that one-third of Americans have just one insurer to choose from if they want an individual plan.
"It's really important that we do something to fix this problem," Ryan said.
But he again said, "I'm not going to put some kind of artificial deadline" on getting a replacement plan done.
Ryan and the Trump administration suffered a humiliating setback in the House last week when they canceled, at the last minute, a vote on their replacement plan, the American Health Care Act.
The bill would have repealed Obamacare taxes, ended out-of-pocket cost subsidies, lowered federal funding of aid that reduces premiums for individual plan customers, and scaled back federal Medicaid spending.
The bill was headed to defeat because of opposition from around 30 Republicans. Some of them said the bill went too far, others not far enough in rolling back provisions in the Affordable Care Act.
Polls showed that the public overwhelmingly opposed the bill, which was projected to lead to 14 million more Americans becoming uninsured next year.
Pelosi on Thursday said Republicans had a "disastrous performance last week."
"The bill was dead. So the American people had spoken: they did not want to repeal the Affordable Care Act," Pelosi said.
Despite the fact that there were moderates among the GOP lawmakers who planned to vote against the bill, Trump has repeatedly blamed the House Freedom Caucus, a group of conservative Republicans, for the failure.
Trump did so again Thursday.
Asked about Trump singling out the caucus, Ryan said: "He's just expressing his frustration."
"You all know that he does that in various forms, including Twitter," Ryan said.
"I understand the president's frustration," Ryan said. "About 90 percent of our conference is in favor of our bill, and 10 percent" are not, he said.
"What I encourage our members to do is keep talking until we get this done, to pass this," Ryan said.
That talking has not gone well, so far.
On Wednesday, members of the moderate Tuesday Group were reportedly resentful that they were being prodded to meet with conservative Republicans to discuss how the repeal-and-replacement effort could move forward.
Axios.com reported that a planned meeting between the Tuesday Group and two groups of conservatives was supposed to occur, but never happened.
A White House source quoted by Axios said, "Welcome to my life the last two weeks. ... It's such a divided conference at the moment it's hard to get things done."