Wilkie's confirmation was approved by the Senate on Monday by a vote of 86-9.
Trump’s previous pick for VA chief, White House physician Ronny Jackson, withdrew his nomination amid allegations of drinking on the job and overprescribing medications.
Wilkie is Trump's third nominee for the Department of Veterans Affairs since taking over the Oval Office. He replaces US Acting Secretary of the Department of Veterans Affairs Peter O'Rourke.
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He previously served as the US Under Secretary of Defense for Personnel and Readiness.