Short-term exposure to PM 2.5 or O 3 can increase mortality risk; however, limited studies have evaluated their interaction. A multicity time series study was conducted to investigate the synergistic effect of PM 2.5 and O 3 on mortality in China, using mortality data and high-resolution pollutant predictions from 272 cities in 2013−2015. Generalized additive models were applied to estimate associations of PM 2.5 and O 3 with mortality. Modification and interaction effects were explored by stratified analyses and synergistic indexes. Deaths attributable to PM 2.5 and O 3 were evaluated with or without modification of the other pollutant. The risk of total nonaccidental mortality increased by 0.70% for each 10 μg/m 3 increase in PM 2.5 when O 3 levels were high, compared to 0.12% at low O 3 levels. The effect of O 3 on total nonaccidental mortality at high PM 2.5 levels (1.26%) was also significantly higher than that at low PM 2.5 levels (0.59%). Similar patterns were observed for cardiovascular or respiratory diseases. The relative excess risk of interaction and synergy index of PM 2.5 and O 3 on nonaccidental mortality were 0.69% and 1.31 with statistical significance, respectively. Nonaccidental deaths attributable to short-term exposure of PM 2.5 or O 3 when considering modification of the other pollutant were 28% and 31% higher than those without considering modification, respectively. Our results found synergistic effects of short-term coexposure to PM 2.5 and O 3 on mortality and suggested underestimations of attributable risks without considering their synergistic effects.