Any pressure on the health service from migration is outweighed by the benefits of EU membership, the NHS England boss has argued.
NHS England boss Simon Stevens said some of its 130,000 European doctors, nurses and care workers could quit the NHS in the wake of a Brexit because of uncertainty over work visas.
He feared any shock to the economy could further hit the NHS's bank balance, after trusts recorded the biggest ever deficit in the history of the health service last week.
Asked about the impact of EU migrants on the NHS, he told the BBC's Andrew Marr Show: "This is not black and white. It clearly is the case that where those migrants are paying taxes that is contributing to the revenues that can afford an expanding NHS.
"When the NHS was set up in 1948 we had a population of 50 million, we're at 65 million now, and the NHS has perfectly, successfully coped with a 15 million expansion in our population; provided it is properly resourced from the proceeds of economic growth it can do that.
"Yes, there's a perfectly legitimate argument to be had on these topics but from the NHS's perspective it is pretty clear that the balance of the advantage is such that the risks would be greater were we to find ourselves in economic downturn, were we to find a number of our nurses and doctors leaving.
"And, indeed, if the pound were affected because a lot of the drug treatments that we buy are priced in euros and dollars, so that could make it more difficult for us to get the treatments we need at an affordable price."
Mr Stevens said he took "very seriously" the warnings made by Bank of England boss Mark Carney of a slowdown of the economy if the UK exits the EU.
He said: "It would be very dangerous if at precisely the moment the NHS is going to need extra funding actually the economy goes into a tailspin and that funding is not there."
He added: "It's been true that for the 68 years of the NHS's history that when the British economy sneezes, the NHS catches a cold. This would be a terrible moment for that to happen at precisely the time the NHS is going to need that extra investment."
Defending his intervention, he said it was "perfectly reasonable" for the NHS to lay out the "practical realities" of how a Brexit would impact the institution in a "balanced, non-sensationalist way".