Managers have said patient care is “on a knife-edge” because of the strike, while NHS Confederation chief executive Matthew Taylor said the number of appointments cancelled, previously suggested to be 250,000, was likely to rise by another 100,000.

They are demanding a pay rise of 35 per cent, which they say is needed to help make up for more than a decade of salary cuts in real terms.

They also argue pandemic backlogs coupled with staff shortages are massively increasing workloads, endangering patients.

“We have had a massive [pay] cut and we are filling more gaps because people are leaving,” said junior doctor Katrina Forsyth, who added she sometimes wept after shifts.

“It’s becoming less safe for patients,” she said from a picket line after finishing a night shift at St. Thomas’ Hospital in London.

The government maintains the British Medical Association’s request is unaffordable, as ministers try to dampen wage demands across the public sector amid stagnant growth and high inflation.

After slowing for three straight months, the Consumer Prices Index shot up to 10.4 per cent in February – close to 40-year highs and more than five times the target set by the Bank of England.

“I hoped to begin formal pay negotiations with the BMA last month but its demand for a 35 per cent pay rise is unreasonable,” said Health Secretary Steve Barclay.

“If the BMA is willing to move significantly from this position and cancel strikes we can resume confidential talks and find a way forward, as we have done with other unions.”

Barclay struck a deal last month with unions representing various health workers, including nurses, to increase pay by five per cent.

Union members are currently voting on whether to accept it.

However, the deal does not cover junior doctors, who comprise around half of all NHS doctors, according to official figures.

Their latest walkout will pile “immense pressures” on the service, NHS England medical director Stephen Powis warned.

“This is a significant set of industrial action that’s going to cause major disruption,” he told BBC radio.

The strike affects the NHS in England but not in the UK’s other regions.

Up to a quarter of a million appointments could be postponed, according to the NHS Confederation, which represents the system in England, Wales and Northern Ireland.

Family doctors are also reported by British media to be closed for appointments for up to a week, as GPs are drafted in to provide cover.

Powis said the NHS is “working very hard” to ensure emergency services are staffed but that cover was “fragile” and “routine care will be affected”.

Phil Sutcliffe, 75, of south London, was among those affected, with his cancer check-up appointment postponed to next month.

But he joined the St Thomas’ Hospital picket line, organised by the BMA.

“These doctors do the most fantastic job for very modest pay … so the government needs to get to the negotiating table and start talking,” he said.

The strike comes as the NHS experiences one of its most severe crises in its 75-year-history, overwhelmed with some 7 million patients waiting for hospital treatment, severely affecting areas such as cardiovascular care.

British Prime Minister Rishi Sunak has made cutting hospital waiting times one of his major priorities amid eroding public satisfaction with an institution that has long been a source of national pride.

The doctors have joined hundreds of thousands of other public sector workers who have gone on strike in Britain, including railway staff, teachers and civil servants.

Disputes in some sectors have been resolved in recent weeks.

Additional reporting by Reuters