US President Barack Obama has nominated budget director Sylvia Mathews Burwell to succeed outgoing Health and Human Services Secretary Kathleen Sebelius.
Mr Obama said Ms Burwell, 48, was an experienced, proven manager.
Ms Sebelius resigned on Thursday, months after the problematic launch of Mr Obama's landmark healthcare overhaul law, which she oversaw.
Mr Obama acknowledged problems under her tenure but said she ultimately "got the job done".
"The final score speaks for itself," Mr Obama said of the estimated 7.5 million people who enrolled in health insurance plans under the Patient Protection and Affordable Care Act before the 31 March deadline.
The 2010 law, nicknamed Obamacare by its detractors, was aimed at extending health insurance to the roughly 48 million Americans who lacked it and at slowing the growth of health costs.
At its heart are online marketplace websites on which consumers and ultimately businesses can shop for insurance.
The websites, called exchanges, were supposed to go live on 1 October but suffered significant, often crippling technical glitches more weeks after the launch.
The botched rollout drew scorn and heaps of criticism from the Republicans, who unanimously opposed the law in 2010 and have since fought to undermine it at every turn.
Republicans see the Affordable Care Act as an inappropriate government intrusion into the healthcare industry.
"She's got bumps, I've got bumps, bruises," Mr Obama said of Ms Sebelius, who fought alongside him in 2009 and 2010 to win passage of the law and later served as a lightning rod for Republican attacks.
The US president had resisted Republican calls for Ms Sebelius to stand down.
Ms Sebelius later made the decision to resign herself, the New York Times reported.
Before becoming health and human services secretary in 2009, Ms Sebelius was governor of Kansas.
Ms Burwell's nomination to lead the Department of Health and Human Services requires Senate confirmation.
She held several positions in the White House and treasury department under President Bill Clinton, and also led global development at the Bill and Melinda Gates Foundation.
"I look forward to carrying on the important work of ensuring that children, families and seniors have the building blocks of healthy and productive lives," she said.