BackgroundEvidence on the acute effect of short-term exposure to nitrogen dioxide (NO2) on years of life lost (YLL) is rare, especially in multicity setting. MethodsWe conducted a time series study among 48 major Chinese cities covering more than 403 million people from 2013 to 2017. The relative percentage changes of NO2-YLL were estimated by generalized additive models in each city, then were pooled to generate average effects using random-effect models. In addition, stratified analyses by individual demographic factors and temperature as well as meta-regression analyses incorporating city-specific air pollutant concentrations, meteorological conditions, and socioeconomic indicators were performed to explore potential effect modification. ResultsA 10 μg/m3 increase in two-day moving average (lag01) NO2 concentration was associated with 0.64% (95% CI: 0.47%, 0.81%), 0.47% (95% CI: 0.27%, 0.68%), and 0.68% (95% CI: 0.34%, 1.02%) relative increments in YLL due to nonaccidental causes, cardiovascular diseases (CVD), and respiratory diseases (RD), respectively. These associations were generally robust to the adjustment of co-pollutants, except for NO2-CVD that might be confounded by fine particulate matter. The increased YLL induced by NO2 were more pronounced in elderly people, hotter days, and cities characterized by less severe air pollution or higher temperature. ConclusionsOur results demonstrated robust evidence on the associations between NO2 exposure and YLL due to nonaccidental causes, CVD, and RD, which provided novel evidence to better understand the disease burden related to NO2 pollution and to facilitate allocation of health resources targeting high-risk subpopulation.