Based on evidence from a powerful earlier eruption, the scientists say such an event could destroy villages and kill people as far as 25 kilometres from its summit.
Dr Giuseppe Mastrolorenzo of the Vesuvius Observatory in Italy, Professor Michael Sheridan, of the University of Buffalo in New York, and colleagues have found compelling evidence that nearly 4000 years ago, Vesuvius produced a most devastating eruption.
The event, called the Avellino catastrophe, destroyed the area of present-day Naples, making Bronze Age farmers flee for their lives.
The researchers first examined the well-preserved remains of Nola, a village about 15 kilometres northeast of the volcano.
Digging the ash layer left by the eruption, they found evidence for "a sudden, en masse evacuation".
"Scenes of everyday life, frozen by the volcanic deposits, testify that people suddenly left the village: the moulds of four huts, with pottery and other objects left inside; skeletons of a dog and nine pregnant goat victims found in a cage; and footprints of adults, children, and cows filled by the first fallout pumice," the researchers write in the current issue of the Proceedings of the National Academy of Sciences.
One kilometre east of Nola, Mastrolorenzo's team found skeletons of a man and a woman buried under a metre of volcanic debris, a dramatic evidence of "their unlucky escape attempt and their death due to suffocation".
The eruption was probably preceded by a warning blast. A 36 kilometre column of ash and gas would have spewed high up into the atmosphere and then rained down, covering about 20 kilometres.
The scientists believe that most of the 10,000 or so inhabitants of the area probably survived the eruption. Indeed, they found thousands of footprints made in the ash, all leading away from the volcano.
Archaeological evidence indicates that some people returned and tried to set up settlements again.
It was a vain attempt, as the deposit of millions of cubic metres of ash and small pumice fragments made the area uninhabitable for hundreds of years.
"We need to incorporate the data of this prehistoric eruption into the hazard plan. This is the most extreme scenario that could impact the city of Naples and its surroundings."
An eruption similar to the Avellino catastrophe today would affect an area much larger than the actual danger 'red zone', which comprises a population of about 600,000 and 18 towns squashed within about a 6 kilometre radius between the volcano and the sea.
Indeed, at least 3 million people live within the area destroyed by the Avellino eruption.
"[Computer modelling shows that] within a radius of at least 12 kilometres from the volcano, the impact force and sedimentation rate of the pyroclastic surge would cause total devastation and mortality, because the inferred dynamic overpressure of surge clouds would exceed even the building strength," say the researchers.
Some 15 kilometres away from the volcano most people would survive, though there would still be risk of suffocating from the fine dust cloud.
"Because a volcanic crisis can start quickly, leaving only a few weeks to months for planning, it is important to use all available data to forecast the scale of potential events," Mastrolorenzo says.
"Catastrophes are often caused by the most extreme events."
A cycle of eruptions
Vesuvius is the only active volcano on the European mainland and erupts dramatically in cycles.
According to Sheridan, while there may not be a high probability that events like the Avellino eruption or the Pompeii eruption will occur in the near future, Italian authorities must still consider those possibilities.
"There was this Bronze Age eruption about 4000 years ago, and then 2000 years ago there was the 79AD event. It seems that just about every 2000 years, there's been a major eruption of this scale at Vesuvius," says Sheridan.
"Using a standard statistical test, there is more than a 50% chance that a violent eruption will happen at Vesuvius next year. With each year that goes by, the statistical probability increases," he says.