Thousands of junior doctors across England are preparing for a second day of strike action where they will provide no emergency care for patients.
More than 20,000 junior doctors are thought to have been on strike on Tuesday as the dispute with the Government over a new contract continues.
Health Secretary Jeremy Hunt has admitted this is likely to be his "last big job in politics" but insisted the Government will not be "blackmailed" into dropping its manifesto pledge of improving seven-day services.
Figures complied by NHS England suggest 78% of junior doctors (21,608) who were expected to be working on Tuesday did not report for duty.
However, NHS England said the figures had not been fully validated and includes those who may be off due to sickness or other reasons.
During the previous strike earlier this month, around 14,600 junior doctors were not at work on each of the two days. Of those, around 12,800 (88%) were actually on strike, with the remainder absent for other reasons such as sickness, NHS England said.
Mr Hunt said on Tuesday that "elements" in the British Medical Association (BMA) had refused to compromise over the new contract, which will be imposed on doctors from August.
He said: "Insofar as it is a political strike, I do think there are some elements - not the majority and certainly not the majority of junior doctors - but there are some elements at the very top of the BMA who are absolutely refusing to compromise."
He added: "This is likely to be my last big job in politics. The one thing that would keep me awake is if I didn't do the right thing to help make the NHS one of the safest, highest quality healthcare systems in the world.
"Health secretaries are never popular. You are never going to win a contest for being the most liked person when you do this job. But what history judges is: did you take the tough and difficult decisions that enabled the NHS to deliver high-quality care for patients? For me, that's what it's about."
David Cameron told ITV News: "It's the wrong thing to do to go ahead with this strike, and particularly to go ahead with the withdrawal of emergency care - that is not right."
Thousands of junior doctors and their supporters marched on the Department of Health in Whitehall on Tuesday evening to protest against Mr Hunt's stance, led by Labour leader Jeremy Corbyn and shadow chancellor John McDonnell.
Mr Corbyn told them it was "utterly contemptible" that Mr Hunt had failed to reach an agreement with junior doctors, despite having "every conceivable opportunity".
He said: "They are the ones who have behaved in the responsible manner of saying they are there to defend the NHS. His response is to try and impose a contract and impose something on them.
"That is no way for a secretary of state to behave towards one of the most crucial elements of the NHS workforce."
The strike is the first time junior doctors have withdrawn full labour, including emergency care, which has been mostly provided by their more senior consultant colleagues.
More than 125,000 appointments and operations have been cancelled and will need to be rearranged as a result of the latest strike, which will run on Wednesday from 8am to 5pm.
Across England on Tuesday, hospitals appeared to cope well, with low waiting times across A&E departments and no urgent calls for doctors to return from the picket lines.
Barts Health NHS Trust, which runs five hospitals in London, said around 11% of about 1,000 junior doctors were working on Tuesday across the trust.
Nick Hulme, chief executive of Ipswich Hospital, tweeted a picture of contingency planning maps for his hospital, adding: "Great work from all the teams."
The BMA junior doctors' committee chairman, Johann Malawana, said the strike represented an "incredibly sad day for doctors, and the rest of society".
He added: "These two days of industrial action mark one of the lowest points in the wonderful history of the NHS."
Mr Malawana said Mr Hunt had refused an opportunity for the strike to be called off by refusing to lift his threat to impose the contract.
Dr Anne Rainsberry, national incident director for NHS England, said: "This is an unprecedented situation and staff across the NHS have made herculean efforts to ensure continued safe services for patients, which is always our top priority.
"However, the escalation of this action does bring heightened risk and we are continuing to vigilantly monitor the picture across the whole of the country."