The Health Secretary has said it will be his "head on the block" if England does not become one of the most successful countries in Europe for preventing premature deaths.
Jeremy Hunt has said the responsibility falls at his feet if local health service commissioners fail to deliver on key objectives set out in the the first contract between the Government and the health service.
Mr Hunt set out a series of goals to improve the nation's health through the first NHS Mandate.
The mandate will form an agreement between ministers and the NHS Commissioning Board (NHSCB), a new body which will supervise the new GP-led commissioning groups that will come into play when the NHS reforms take effect next year.
The document says around 20,000 lives a year would be saved in England if mortality rates were reduced to the best level in Europe.
It calls on the NHSCB to make "measurable progress" towards making England one of the most successful countries in Europe at preventing people from dying prematurely.
"If the board does not succeed, in the end it will be my head on the block because I am the one who has negotiated this mandate with the board," said Mr Hunt.
"Ministers appointed people to the board and we believe it is the structure that has the best possible chance to leading to dramatic improvements in the NHS. In the end we are responsible as ministers for the structures that we have set up."
Ministers are hailing the mandate as a landmark for the NHS by ensuring the health service is held to account. They said the contract will mean ministers will not micro-manage the health service from Whitehall.
Mr Hunt claims the document gives frontline health professionals more power and independence to deliver care.