BackgroundEnvironmental risks accumulate in cities, including polluted air and health disparities, but these risks can be reduced through scientific city planning. The purpose of this study was to investigate the global burden of premature mortality attributable to NO2 exposure in urban areas and the role of the built environment in this regard. MethodsAn approach based on health impact assessment was used to estimate the premature mortality burdens associated with NO2 exposure in 13,169 urban areas around the world using globally gridded NO2 and population estimates, baseline mortality, and epidemiologically derived exposure-response functions. We used the most recent WHO recommended value (i.e.,10 μg/m3) as a counterfactual concentration. Finally, the relationship between the characteristics of the built environment at the city level and the burden of NO2-related mortality was evaluated. ResultsWorldwide, 549,715(95%CI: 276204–815,023) cases of death attributable to NO2 exposure in urban areas could be prevented if compliance with the latest WHO guideline, accounting for 2.7 % (95%CI:1.4 %–4.0 %) of total mortalities in 2019. Across cities around the world, the age-standardized mortality rate (per 100,000 people) attributable to NO2 exposure ranged from 51.3 (95%CI:25.8–76.0) in Central Asia to 3.4(95%CI: 1.7–5.1) in Oceania. Although there was a significant decrease in premature mortality attributable to NO2 exposure globally, considerable regional heterogeneity exists, with cities in Central Asia and Andean Latin America in particular exhibiting an upward trend. Further, we discovered a positive association between population density and street connectivity with mortality attributable to NO2. While the increase in green and blue space were significantly associated with a lower NO2-associated mortality. ConclusionThe findings of this study provided a comprehensive understanding of the premature mortality burden due to NO2 in cities throughout the world and the role that urban planning policies can play in reducing the health burden associated with air pollution.