IN large eruptions, Vesuvius has generated catastrophic avalanches of tephra and hot gases, such as those that destroyed Pompei and Herculaneum in AD 79, and Torre del Greco and surrounding towns in 1631(1-12). These avalanches (pyroclastic surges and flows) are produced from collapses of the eruptive column, and can travel at > 100 m s-1, with temperatures exceeding 800-degrees-C. In 1944 Vesuvius ended its most recent cycle of activity, which had begun with the explosive eruption of 1631. Here we use numerical simulations to assess the hazards posed by the pyroclastic flows that are likely to accompany the onset of the next cycle of activity. We examine three different scales of eruption, and use vent conditions established by modelling magma ascent along the conduit13,14. Our results indicate that large- and medium-scale eruptions can produce complete destruction in the 7 km radius around the volcano (an area in which one million people live and work) in about 15 minutes or less, and that only small-scale eruptions can be arrested by the topographic relief of Monte Somma.