Cynthia Bower announced her resignation on Thursday as the DH released a critical performance review of the CQC.
A CQC spokesman said GP registration would be unaffected by Ms Bower's departure, but GPC negotiator Dr Chaand Nagpaul warned a change in leadership could trigger a change in policy. 'This clearly does create a break,' he said.
'We will need to work with the CQC, with any successor, and make sure any concerns about the registration process are heard.'
The DH-led performance and capability review said the CQC had not done enough to manage risks during the early years of its operation.
It said the CQC had not made its role clear to health and care providers, patients and the public.
The review set out a number of recommendations for the CQC, calling for an increase in the number of board members, greater access for frontline inspectors to doctors and nurses, and assurances that there are enough inspectors to meet future demand.
After her resignation, Ms Bower said: 'After almost four years leading the CQC, I feel that it is now time to move on.
'I am pleased that the DH performance and capability review, published today, recognises the scale of what has been achieved - and in particular the significant improvements made over the last nine months.'
Ms Bower will remain in post until autumn 2012.