The NPSA refused to reveal details of the arrangements. However, the pair's exit followed last year's report by the Commons public accounts committee, which called the agency 'dysfunctional'.
Sue Osborn and Susan Williams, both 54, have shared the role at the NPSA since 2001.
Known as the 'two Sues', the women each worked for three days a week and received an annual salary of between£90,000-£95,000.
Ms Osborn declined to elaborate on the reasons for the move - but told HSJ: 'We have agreed to early retirement. We still see the NHS as a wonderful place with a set of hugely talented people, which isn't said enough.
'Neither of us have any set plans - we'll be looking at a range of opportunities, including job-shares.'
In an official statement, Ms Osborn and Ms Williams said they felt honoured to have been joint chief executives of the NPSA.
Commenting upon their retirement, NPSA chair Lord Patel recognised their contribution in introducing the national reporting and learning system.