The historic strike will affect almost all planned care as consultants who began their industrial action on Tuesday are joined by junior doctors on Wednesday.
That means there will only be Christmas Day levels of staffing from 7am Wednesday meaning emergency care will be provided but most routine work will be stopped.
Matthew Taylor, chief executive of the NHS Confederation, said: “The worst-case scenario of NHS consultants and junior doctors walking out together has become a terrible reality. This is likely to be the biggest walkout the NHS has ever seen, will cause serious disruption, and put patients at the highest level of risk in living memory.
“Leaders are concerned this dangerous situation is being underestimated by the government, telling us this feels much different and more complex than previous strikes, with most reporting greater difficulties in rota planning and having to cancel huge numbers of elective operations and appointments in advance.
“This is much worse than before as we’re now seeing patients who have already had an operation cancelled due to industrial action be hit again with a cancellation to their rescheduled appointment.
“Leaders have also told us that this time round a higher number of operations and appointments for cancer patients are being cancelled, meaning that some of the very sickest patients maybe suffering the most.”
As well as being out on Wednesday, junior doctors will continue to strike on Thursday and Friday this week.
Both groups will then strike on October 2, 3 and 4 which will again see Christmas day cover levels of service.
The NHS is now in its tenth month of industrial action which has so far seen more than 885,000 inpatient and outpatient appointments rescheduled.
Previous industrial action by consultants last month saw 45,800 appointments disrupted and around 6,000 staff off per day due to the strike.
Despite that, NHS bosses have said the public should continue to use health services as they usually would –- using 999 and A&E in life threatening situations and using 111 online for other health concerns.
GPs and pharmacies can be used by the public for health advice and appointments as normal.
NHS national medical director professor Sir Stephen Powis said: “The NHS has simply never seen this kind of industrial action in its history. This week’s first ever joint action means almost all planned care will come to a stop, and hundreds of thousands of appointments will be postponed, which is incredibly difficult for patients and their families, and poses an enormous challenge for colleagues across the NHS.
“We’re very grateful to the public for using the NHS wisely during this period when we will be prioritising emergency care. In a life-threatening situation, use 999 and A&E as normal, but for everything else, use 111 online or use services in the community which are largely unaffected, like GPs and pharmacies. Patients who have an appointment and who haven’t been contacted should attend as normal.”