Fallout of ballistic blocks and bombs ejected from eruptive vents represents a well-known hazard in areas proximal to volcanoes (mostly <5 km from the vent). However, fallout of large clasts sedimenting from plume margins that extend to medial areas and have the potential to produce severe injuries to people and cause damage to infrastructure, is often overlooked. Recent eruptive events at Mount Etna (Italy) provide a clear example where large-clast fallout from plume margins (>5 cm) has posed a real threat both to the many visitors reaching the summit area and to local infrastructure, and, therefore, has been selected as a case study. To quantify this hazard, a new particle sedimentation model was calibrated with field data and then used for probabilistic hazard assessments. For a fully probabilistic scenario the hazard zone covered 72 km2 and included some 125 km of paths and roads, as well as 15 buildings. Evacuation on foot to a safe area was estimated at almost 4 h, but this could be reduced to less than 3 h if two shelters were provided. Our results show the importance of integrating probabilistic hazard analysis of large-clast fallout within effective strategies of risk management and reduction, especially in the case of volcanoes where visitors can reach the summit areas.