Paul O'Connor's resignation from his position at Birmingham Children's Hospital was tendered with immediate effect on Saturday (7 March).
His decision to quit comes ahead of the publication of a report by the Healthcare Commission, which investigated the hospital after concerns were raised by a number of its own doctors.
In a statement, Birmingham Children's Hospital NHS Foundation Trust said: "The trust can confirm that Paul O'Connor, chief executive, has tendered his resignation with immediate effect. He has not been removed from his position.
"Further statements will be released in due course. However, at this stage, we can make no further comment."
The investigation was triggered on the back of a leaked report, which surfaced in November, that claimed staff at Birmingham Children's Hospital had previously raised concerns about the quality of care, which were not taken seriously.
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