The large explosive eruption of Merapi volcano, Indonesia, in 2010 presented a key, and rare, opportunity to study the impacts of a major explosive eruption in a densely populated area. Pyroclastic density currents (PDCs) produced throughout the 2010 eruption were unusually destructive, causing near complete devastation across a 22km2 swath of the densely populated southern flanks and casualties to the end of their runout at 15.5km from the volcano. The majority (>120) of the more than 200 fatalities occurred more than 12km from the volcano, where many people were caught in PDCs as they were evacuating. The 2010 eruption (VEI 4) exhibited a range of PDC behaviour in a complex multi-stage event that marked a change in eruption behaviour at Merapi, being the first eruption of this magnitude and style since 1872. This shift in style may mark a change in regime, and so understanding the potential impact of such large explosive eruptions is essential for future risk-assessment at Merapi. We describe a new impact assessment methodology that allowed us to collect important empirical geological, damage and casualty information and reconstruct impact dynamics associated with the PDCs. In contrast to previous PDC impact studies, we combined remote, field, laboratory and GIS assessments and were able to enter the affected areas safely and before their disturbance by rains or human activity. By integrating the results of our geological, damage and medical studies, we could reconstruct the spatial and temporal dynamics of the PDCs and their main hazard characteristics. Our interdisciplinary methods and preliminary findings are discussed here. In the areas damaged by PDCs, we used empirical damage data and calculations of material and structural resistance to lateral force to estimate approximate dynamic pressures. Dynamic pressures associated with the 5 November paroxysm exceeded 15kPa more than 6km from source and rapidly attenuated over a distance of less than 1km at the end of the PDC runouts. Analysis of thermal indicators, such as deformed plastic, and correlation with information on burns injuries and fires provided estimates of ambient temperatures associated with the PDCs. Even at the relatively low temperatures estimated for the PDCs (200–300°C) they were lethal to people inside as well as outside buildings, in part because of the building design that enabled the PDCs to rapidly infiltrate inside. Such detailed quantitative data can be used to support numerical PDC and impact modelling and risk assessment at dome-forming volcanoes, providing an improved understanding of the complexity of PDCs and their associated impacts on exposed populations.