Eric Munson said he will leave his position as president and chief executive of UNC Hospitals.
Munson said he is resigning at the health system board's request.
Munson, who will receive a two-year buyout worth more than $384,000 a year, will remain as a senior adviser.
The chief executive of Rex Health Care in Raleigh, Gary Park, will take Munson's job.
Munson said in a statement that he resigned "with a sense of melancholy and resolve.
"I look forward to the opportunity to provide whatever insight, advice and institutional memory may be useful to the new leadership team."
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