By Louise Radnofsky 

The U.S. Senate on Thursday voted 78-17 to place Sylvia Mathews Burwell in charge of the Department of Health and Human Services, which steers implementation of the Affordable Care Act.

The confirmation of Ms. Burwell, 48, as health and human services secretary, marks a shift for an agency that has been headed by former governors for the past 14 years. Kathleen Sebelius, the current secretary and former Kansas governor, focused for much of her five years in the job on selling the 2010 health law to the American public.

Ms. Burwell, by contrast, brings management experience to the job that former colleagues say will help her lead the agency's big projects. Chief among them is ensuring that HealthCare.gov operates smoothly during this fall's insurance enrollment period after a disastrous rollout last year.

Ms. Burwell, who will be leaving the job of director of the Office of Management and Budget, previously had high-level positions in the Clinton White House, Gates Foundation and Walmart Foundation, but has never held elected office.

"She goes very, very deep on the details, but she has a very broad policy lens," said Leslie Dach, the former executive vice president of corporate affairs for Wal-Mart, who wooed her in 2011 to become president of the company's foundation. She worked there for just over a year before coming back to Washington.

Those traits will be tested at the Department of Health and Human Services, a 78,000-employee agency that, in addition to wrestling with enacting the Affordable Care Act, also oversees Medicare, Medicaid, disease control, food and drug regulation, and funding for medical research in the U.S.

Patty Stonesifer, the former chief executive officer of the Gates Foundation, and Helene Gayle--the former head of the foundation's AIDS, tuberculosis and reproductive health programs--said that Ms. Burwell's work there included helping the foundation figure out how to make strategic funding investments and wrapping up grants and programs when their life span was up.

Ms. Burwell has some experience dealing directly with health systems, having served on the board of University of Washington Medical Center from 2002 to 2005. During that time, the hospital went through a major overhaul of its information technology. It was also trying to review missteps and set up a compliance program in the wake of a federal investigation into Medicare billing problems in the 1990s.

People who have worked with Ms. Burwell have described her deft political skills, which have typically been used outside of the limelight. Those traits were on display in her path to confirmation, which appeared to be eased by her ability to forge relationships with key senators. Several Republicans had been vocal in criticism of the Obama administration, but praised her.

Among them were Utah Sen. Orrin Hatch, Arizona Sen. John McCain and Oklahoma Sen. Tom Coburn, as well as Georgia Sen. Johnny Isakson. Mr. Isakson said at the outset of her confirmation process that he wouldn't let Ms. Burwell leave the Office of Management and Budget until he was satisfied with her answers about the agency's role in approving an expansion project for the Port of Savannah.

She also had the vocal backing of a roster of Democratic politicians, including Sens. Jay Rockefeller and Joe Manchin and Rep. Nick Rahall, all from her home state of West Virginia.

Write to Louise Radnofsky at louise.radnofsky@wsj.com

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