The NHS could save at least £85m a year through more efficient prescribing of statins, drugs which lower cholesterol, the government says.
Statins differ in price
The health service spends about £600m a year on the drugs.
Costs of statins depend on whether they are a brand or are a cheaper generic version.
Ministers said if the NHS used generic drugs in 69% of cases - as a quarter of trusts do - the saving would be made, but experts said lives could be risked.
Statins are currently used by nearly 2m people in the UK, and the cost to the NHS has risen by 150% in the last five years.
The government looked at data from primary care trusts from July to September - the second quarter of this financial year.
It found a quarter of trusts used generic versions of statins called pravastatin and simvastatin in over two thirds of cases and it called for others to follow suit.
Health Minister Andy Burnham said: "As new drugs become available, the local NHS will increasingly have to look closely at the resources it spends on common treatments to ensure it is getting value for money.
"Statin prescription is one of the areas that can release the most savings which can be ploughed back into patient care.
"The figures I'm publishing today show that productivity gains are already being delivered by many PCTs and demonstrate to other parts of the NHS the savings they could make.
"Clinicians can help to treat more patients by prescribing one of the lower cost drugs where it is clinically appropriate."
But Professor Peter Weissberg, medical director of the British Heart Foundation, said: "The problem is that the two generic versions available to the NHS are not as potent as some of the newer, more expensive statins coming on to the market.
"So it would not be right to have a target like this when it could put lives at risk.
"It is much better to say to doctors they should look to use generic versions but monitor a patients' reaction to see that their cholesterol is coming down."