Junior doctors have pledged to fight on after Jeremy Hunt announced he will impose a new contract on thousands of medics in England.
The British Medical Association (BMA) said it would "consider all options", raising the possibility of further strikes in the battle over pay and conditions.
Royal colleges and unions have expressed dismay at the Health Secretary's move, which comes after weeks of deadlock between the BMA, Government officials and NHS Employers.
Dr Johann Malawana, the BMA's junior doctor committee chairman, said: "The decision to impose a contract is a sign of total failure on the Government's part."
He accused Mr Hunt of "ploughing ahead with proposals that are fundamentally unfair". The BMA has already staged two strikes.
He said: "The Government's shambolic handling of this process from start to finish has totally alienated a generation of junior doctors - the hospital doctors and GPs of the future - and there is a real risk that some will vote with their feet.
"Our message to the Government is clear - junior doctors cannot and will not accept a contract that is bad for the future of patient care, the profession and the NHS as a whole, and we will consider all options open to us."
One possibility is of further strike action while there are also suggestions of legal action. Some junior doctors may refuse to sign new contracts which are due to be implemented from August.
The major sticking point has been over weekend pay and whether Saturdays should attract extra "unsocial" payments.
Currently, 7pm to 7am Monday to Friday and the whole of Saturday and Sunday attracts a premium rate of pay for junior doctors.
But the Government wants the Saturday day shift to be paid at a normal rate in return for a hike in basic pay.
The BMA has rejected this and has urged Mr Hunt to accept its proposal to reduce the 11% rise in basic pay offered by ministers and instead have better premium rates on Saturdays.
The Government drafted in Sir David Dalton - chief executive of Salford Royal NHS Foundation Trust - to broker a deal but the deadlock could not be broken.
In a statement to the Commons, Mr Hunt said the BMA had proved "unwilling" to show flexibility and compromise.
He said that with the backing of major NHS groups including NHS Employers and NHS England, Sir David "has asked me to end the uncertainty for the service by proceeding with the introduction of a new contract that he and his colleagues consider both safer for patients and reasonable for junior doctors".
"I have therefore today decided to do that."
Mr Hunt said the new contract will mean an increase in basic salary of 13.5% and that three quarters of doctors will see their take-home pay increase.
No doctor working contracted hours would see a pay cut while too many night shifts and long shifts will also be limited.
Under the new contract, 7am to 5pm on Saturdays will be regarded as a normal working day.
Doctors working one in four or more Saturdays will receive a pay premium of 30%.
Mr Hunt said: "While I understand that this process has generated considerable dismay among junior doctors, I believe that the new contract we are introducing - shaped by David Dalton and with over 90% of measures agreed by the BMA - is one that, in time, can command the confidence of both the workforce and their employers."
He said there was an "overwhelming consensus" that the standard of weekend services is "too low".
"The lessons of Mid Staffs, Morecambe Bay and Basildon in the last decade is that patients suffer when governments drag their feet on high hospital mortality rates, and this Government is determined our NHS should offer the safest, highest quality care in the world."
Shadow health secretary Heidi Alexander told Mr Hunt: "Imposing a contract is a sign of failure, it's about time you realised that."
BMA council chairman Mark Porter said the move would be seen as "threatening and dictatorial" and warned nurses and other clinical staff to prepare for similar treatment.
Asked if there could be more strikes, he told the programme: "We are going to reflect on what it is our members want us to do."
He went on: "I am accepting that the basis of the game has changed, in that the Government has taken this - what no doubt they see as decisive but which many in the NHS and the public sector will see as threatening and dictatorial - (step)."
Labour leader Jeremy Corbyn, who surprised commentators by failing to raise Wednesday's strike with David Cameron during Prime Minister's Questions, said: "Jeremy Hunt's decision to impose a contract on junior doctors is provocative and damaging."