BACKGROUND: Relative risk estimates for long-term ozone (O3) exposure and respiratory mortality from the American Cancer Society Cancer Prevention Study II (ACS CPS-II) cohort have been used to estimate global O3-attributable mortality in adults. Updated relative risk estimates are now available for the same cohort based on an expanded study population with longer follow-up. OBJECTIVES: We estimated the global burden and spatial distribution of respiratory mortality attributable to long-term O3 exposure in adults >/=30y of age using updated effect estimates from the ACS CPS-II cohort. METHODS: We used GEOS-Chem simulations (2x2.5 masculine grid resolution) to estimate annual O3 exposures, and estimated total respiratory deaths in 2010 that were attributable to long-term annual O3 exposure based on the updated relative risk estimates and minimum risk thresholds set at the minimum or fifth percentile of O3 exposure in the most recent CPS-II analysis. These estimates were compared with attributable mortality based on the earlier CPS-II analysis, using 6-mo average exposures and risk thresholds corresponding to the minimum or fifth percentile of O3 exposure in the earlier study population. RESULTS: We estimated 1.04-1.23 million respiratory deaths in adults attributable to O3 exposures using the updated relative risk estimate and exposure parameters, compared with 0.40-0.55 million respiratory deaths attributable to O3 exposures based on the earlier CPS-II risk estimate and parameters. Increases in estimated attributable mortality were larger in northern India, southeast China, and Pakistan than in Europe, eastern United States, and northeast China. CONCLUSIONS: These findings suggest that the potential magnitude of health benefits of air quality policies targeting O3, health co-benefits of climate mitigation policies, and health implications of climate change-driven changes in O3 concentrations, are larger than previously thought. https://doi.org/10.1289/EHP1390.