Andrew Lansley has accused midwives and nurses of opposing NHS reform for "political" reasons.
Following the Royal College of Nursing (RCN) and the Royal College of Midwives (RCM) calling for the health and social care bill to be scrapped, the health secretary said unions wanted to "have a go at the government".
"What has changed in the last few weeks? Well, the Royal College of Nursing basically has two sides to it. One is about being a professional association for nursing the other is about a trade union," Lansley told BBC Radio 4's Today programme
"Frankly I think the only thing that has changed is they want to have a go at the government because of the trade union aspect."
"They're having a go at us about this and it's purely, in that sense, a political operation on the part of the RCN."
The Doctors union, the British Medical Association, has already said it opposes the bill.
The RCN said the government's proposed changes are a "serious threat to the NHS".
RCN head Dr Peter Carter hit back: "We utterly reject the claim that the RCN's decision to oppose the Health and Social Care Bill was based around the proposed pension changes.
"Nurses want to provide the highest possible standards of patient care and it is at the heart of everything they do.
"However, members up and down the country are telling us that this Bill is seriously destabilising the NHS.
"Equally, we know that tens of thousands of posts are being lost throughout the NHS, which is putting patient care in jeopardy and that there is now a fundamental imbalance between competition and collaboration within the NHS."
Andy Burnham, the shadow health secretary, said: "It's hard to see how David Cameron can carry on with his Health Bill after the decisions taken by the Royal College of Nursing and the Royal College of Midwives.
"Doctors, nurses and midwives are now standing together in outright opposition to his plans to turn the NHS into a market-based system.
"A reorganisation on this scale needs a professional consensus for it to succeed. A year since the Bill was introduced it is abundantly clear that the government's plans have failed to build that.
"We agree with the RCN's assessment that the risks of proceeding with these plans are greater than the risks of dropping the Bill.
"It is time to put the NHS first. The government must listen to patients and NHS staff and put this Bill out of its misery."