Nursing union leader Pat Cullen has told the Government the next round of pay talks must begin with discussions of a double-digit pay rise.
In a fresh escalation of the bitter wage dispute, the Royal College of Nursing (RCN) General Secretary said talks must "start off" above 10% or risk strikes running to Christmas.
RCN members will begin voting on May 23 for further strike action after the union's six-month mandate expired at the beginning of the month.
Ms Cullen said she had "underestimated" nurses after members rejected the Government's 5% pay offer - despite the union calling for them to accept it.
She told the Sunday Times that Health Secretary Steve Barclay must restart negotiations and said the talks need to “start off in double figures”.
Ms Cullen said: "They (ministers) owe that to nursing staff not to push them to have to do another six months of industrial action right up to Christmas."
"It's just not right for the profession," she added.
"It's not right for patients. But whose responsibility is it to resolve it? It is this government."
Ms Cullen originally pushed for a 19% pay hike before advising members to accept the Government's 5% offer - which they rejected.
The majority of other unions on the NHS Staff Council, which acts as a bargaining unit, have accepted the deal.
"It's not so long ago since the Prime Minister went on the media and very publicly said nurses are an exception," Ms Cullen said.
"I would totally agree with him... they should be made an exception because they are exceptional people."
An RCN spokesperson said: “The negotiations covered two financial years which resulted in a consolidated NHS pay increase of 9 per cent.
"When our members rejected that, it is clear they expect an offer into double figures.”
Ms Cullen, a mental health nurse, 58, from Co Tyrone, said patient safety was "at the centre of everything that we do".
"We will do nothing that will add further risk to the patients that we look after," she said, saying increased pay would see nurses return to the profession and ease a staffing crisis.
"The truth is that patient safety cannot be guaranteed on any day of the week. How could you guarantee patient safety when you have 47,000 nurses from your workforce every single day and night?"
She warned Prime Minister Rishi Sunak not to take her members lightly.
"Looking back on this pay offer, I may personally have underestimated the members and their sheer determination," she said.
"I think what I would be saying to the Prime Minister, Rishi Sunak, is 'Don't - don't make that same mistake, don't underestimate them'.
"Nurses believe it's their duty and their responsibility because this government is not listening to them on how to bring it (the NHS) back from the brink and the message to the Prime Minister is that they are absolutely not going to blink first in these negotiations."
Energy Secretary Grant Shapps branded her stance "rather confusing" and said nurses should have accepted the pay deal.
He told Sky's Sophy Ridge on Sunday: "Pat Cullen just recently was encouraging her members to accept a pay deal that was put on the table that would see £5,000 go into the pockets this year of hard working nurses.
"I thought this was a great settlement, I thought it was terrific that it had been reached.
"It's frankly rather confusing now that having encouraged her members to accept that deal, she seems to now be coming back and saying the opposite."
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