US Health and Human Services Secretary Kathleen Sebelius is resigning after overseeing the botched rollout of President Barack Obama's signature healthcare law.
Ms Sebelius, 65, became the public face for the problem-plagued start to the enrolment period for the Affordable Care Act or "Obamacare".
The law was meant to reduce the number of Americans without health insurance and cut into massive US healthcare costs.
When enrolment opened in October, the federal HealthCare.gov website used by consumers in 36 states failed to work for weeks.
The White House called in a team of management and technology experts to fix the site, which began working more or less smoothly by December.
Even as she took responsibility for the failures, Mr Obama stuck by Ms Sebelius, brushing aside pressure to fire her.
"Hold me accountable for the debacle. I'm responsible," Ms Sebelius said at a hearing on 30 October.
The enrolment period was ultimately successful, surpassing the 7m figure the Obama administration had predicted.
Ms Sebelius's departure removes one issue for critics, as Mr Obama and Democrats try to retain control of the US Senate in November midterm elections.
However, Republicans continue to see problems with the Affordable Care Act as a winning issue.
"If the Obama people thought this was going to calm the waters, I think they misread it," said David Yepsen, director of the Paul Simon Public Policy Institute at Southern Illinois University.
"I think it's just going to embolden Republicans," he said.
The start on 1 October of new Obamacare health insurance marketplaces has been condemned by Republicans as a step toward socialised medicine.
Polls suggest "Obamacare" remains unpopular.
In March, 46% of people said they had an unfavourable view of the law, while 38% said they liked it, according to the Kaiser Family Foundation.
Mr Obama has chosen Sylvia Mathews Burwell, his budget director, to replace Ms Sebelius, the White House said.
Ms Burwell will have to manage the programme through its next major challenges in the height of elections season.
But Ms Burwell has a "tall order" to fix all the detailed issues with the law, and improve its standing among voters, Mr Yepsen said.
Ms Sebelius, a former governor of Kansas, told Mr Obama in early March she wanted to leave the administration, a White House official said.
"She believed that once open enrolment ended it would be the right time to transition the department to new leadership," the official said.
Ms Sebelius remains on the job until Ms Burwell is confirmed by the Senate, an administration official said.