Anthropogenic secondary organic aerosol (ASOA), formed from anthropogenic emissions of organic compounds, constitutes a substantial fraction of the mass of submicron aerosol in populated areas around the world and contributes to poor air quality and premature mortality. However, the precursor sources of ASOA are poorly understood, and there are large uncertainties in the health benefits that might accrue from reducing anthropogenic organic emissions. We show that the production of ASOA in 11 urban areas on three continents is strongly correlated with the reactivity of specific anthropogenic volatile organic compounds. The differences in ASOA production across different cities can be explained by differences in the emissions of aromatics and intermediate- and semi-volatile organic compounds, indicating the importance of controlling these ASOA precursors. With an improved model representation of ASOA driven by the observations, we attribute 340 000 PM2.5-related premature deaths per year to ASOA, which is over an order of magnitude higher than prior studies. A sensitivity case with a more recently proposed model for attributing mortality to PM2.5 (the Global Exposure Mortality Model) results in up to 900 000 deaths. A limitation of this study is the extrapolation from cities with detailed studies and regions where detailed emission inventories are available to other regions where uncertainties in emissions are larger. In addition to further development of institutional air quality management infrastructure, comprehensive air quality campaigns in the countries in South and Central America, Africa, South Asia, and the Middle East are needed for further progress in this area.