Junior doctors - all medics below consultant level - are providing emergency care only in the 24-hour walkout, which started at 8am.
It is the second strike by the British Medical Association (BMA) in a bitter dispute with the Government over a new contract.
The first, in January, led to thousands of operations, procedures and appointments being cancelled across the NHS.
Today's action is causing similar disruption, with analysis by NHS England showing 1,150 planned inpatient procedures have been cancelled, alongside 1,734 day procedures.
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Thousands more appointments could be affected.
Sir David Dalton - chief executive of Salford Royal NHS Foundation Trust, who has been drafted in by the Government to broker a deal - held last-minute talks with BMA representatives and officials from NHS Employers in a bid to avert the strike.
However, the informal talks concluded yesterday with no resolution.
The major sticking point in the dispute is over weekend pay and whether Saturday should be largely classed as a normal working day.
Currently, 7pm to 7am Monday to Friday and the whole of Saturday and Sunday attract a premium rate of pay for junior doctors.
An offer from the Government in November said doctors would receive time-and-a-half for any hours worked Monday to Sunday between 10pm and 7am, and time-and-a-third for any hours worked between 7pm and 10pm on Saturdays and 7am and 10pm on Sundays.
But in its latest offer, ministers said that as part of an overall agreement, a premium rate of pay could kick in from 5pm on Saturdays rather than 7pm, and at 9pm Monday to Friday.
This offer was rejected by the BMA, which then put forward a proposal that would have seen doctors' basic pay rise by about half the 11% offered by ministers in return for Saturday not to be treated as a normal working day.
The union argued it would have been cost-neutral, meaning the Government would not pay any more than the £5 billion currently spent on junior doctor salaries.
But the Government blocked that deal.
Dr Johann Malawana, the BMA's junior doctors' committee chairman, tweeted on Wednesday morning: "We presented fully costed & working solution that was rejected due to pride & politics."
According to The Independent, an online poll of 1,045 medics found 922 were "prepared to consider resignation" should Health Secretary Jeremy Hunt follow through on his vow to impose the contract.
A poll has found that two-thirds of adults in England support the strike. The survey of more than 800 people, conducted by Ipsos Mori and the Health Service Journal, found that 66% supported the action, while 64% said the Government was more at fault for the dispute continuing this long and 13% said the blame lies with junior doctors. Nearly a fifth (18%) believed both sides were equally at fault.
Dr Anne Rainsberry, national incident director for NHS England, said: "The NHS is doing everything possible to minimise the impact of this regrettable strike which will delay care for thousands of patients at a time of year when service pressures across the health service are already at their highest.
"We will monitor the situation across the country to ensure plans are in place, and people are ready to respond to any significant increases in pressure in any region over the period of this strike."
Dr Malawana has urged strikers to contact the BMA if they receive requests from hospitals to return work.
During the last strike, health bosses in Sandwell declared an incident and ordered strikers off the picket lines and back to work.
In a video message posted on the BMA's Twitter account, Dr Malawana urged doctors to contact the BMA for advice and pointed to a protocol between NHS England and the union about returning to work only if there is a "major unpredictable incident".
Chris Hopson, chief executive of NHS Providers, told BBC Radio 4's Today programme the Government should consider imposing a new contract.
"Just like across a whole swathe of our economy, we are moving to providing 24 hours a day, seven days a week services," he said.
"Just as we have done in local government, just as we have done in retail, just as we have done in prisons and the police force, we need to modernise junior doctors and the other contracts so we have contracts that enable the NHS to provide 24 hours a day, seven days a week care.
"I think our members are saying to us this really does need to reach a conclusion. I think the ideal conclusion would be for employers to make a fair and final reasonable offer and for the BMA to accept it.
"If the BMA doesn't accept it I think our members are saying to us that the Secretary of State has to find a way to bring this to a conclusion.
"We cannot carry on like this. We need to bring this to a conclusion. If the BMA won't accept a fair and reasonable offer then, yes, it is legitimate and sensible for the Secretary of State to consider imposition."