Extra controls are needed to make sure hospital bosses are not manipulating services to meet targets, a study says.
London School of Economics researchers said targets had helped to improve NHS performance in England.
But they warned systems were needed to stop "gaming" - where efforts to hit targets damage other services, the British Medical Journal reported.
They said the A&E wait target had harmed other hospital services, but the government said targets were working.
Researchers highlighted targets which have improved access to services, such as the maximum four-hour wait in A&E.
"What we have to do is ask whether the benefits are worth the consequences and be alert for problems that may arise"
In 2002, before the target was set, 23% of patients spent longer than four hours in A&E, but by 2004 this had fallen to 5%.
There have also been improvements in response times by ambulance trusts, as well as waiting lists for patients needing elective surgery.
But they also said they had led to gaming, citing the four-hour A&E target which had meant extra staff were brought into casualty when performance was being measured, meaning operations elsewhere in the hospital had to be cancelled.
Another gaming method involved patients having to wait in an ambulance outside A&E until staff were confident they could meet the target.
Professor Hood said: "Nobody would want to return to the NHS performance before the introduction of targets, with over 20% of patients spending more than four hours in accident and emergency and patients waiting more than 18 months for elective admission.
Sanctions
"So how can we maximise the social benefits and minimise the costs of a regime of targets and sanctions?"
The researchers suggested introducing more uncertainty into the way that performance was assessed to make gaming more difficult and an independent body to investigate how genuine reported improvements were and what their cost to other services had been.
Dr Richard Lewis, a researcher at the King's Fund health think-tank, agreed targets had had unintended consequences.
"You only need look at the problems with booking advanced GP appointments because of the 48-hour wait target to see there can be problems.
"What we have to do is ask whether the benefits are worth the consequences and be alert for problems that may arise."
A Department of Health spokesman said: "NHS targets are working. They are driving forward the recruitment of more doctors, nurses and other NHS staff and helping deliver the fastest access to healthcare."
But he also said the government was now looking to move away from a target-based culture, with the number of targets reducing from 62 to 20.
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