The Central Bank's director of credit institutions and insurance Fiona Muldoon is leaving the bank.
She will depart in May next year.
In a statement, the Central Bank said Ms Muldoon had resigned her position.
Ms Muldoon said she hoped she had made a meaningful contribution towards resolving some of the challenges besetting the financial services industry and to the Central Bank during her time there.
Central Bank Governor Patrick Honohan said she had "great vision" and "was a real agent of change."
Ms Muldoon did not make any comment on her future plans.
Last year Ms Muldoon gained attention for her sharp criticism of the way mortgage lenders were dealing with indebted homeowners.
In a speech to the Irish Banking Federation in October 2012, she accused banks of paying "lip service" to the idea of making progress in dealing with arrears, adding that she saw "too much activity and not enough outcome."
Ms Muldoon's departure is the latest in a series of high-profile resignations at the bank.
Financial regulator Matthew Elderfield and chief economist Lars Frissel also left the Bank earlier this year.
"A lot of people have come in and naturally some will stay longer than others. We have strength in depth and are confident we can deliver on our mandate," Central Bank Governor Patrick Honohan told reporters.