Abstract Background Air pollution is a major environmental risk to human health, contributing to premature death and disease. Nitrogen dioxide (NO2) is a pollutant of significant public health concern, associated with increased risks of all-cause mortality, particularly in cardiovascular and respiratory deaths. In 2021, NO2 exposure exceeding the World Health Organization Air Quality Guidelines resulted in 69,000 deaths in the European Union. This study aims to estimate the impact of ambient NO2 exposure on ischemic heart disease (IHD) in Portugal, from 2011 to 2021, estimated in years of life lost (YLL). Methods Data on ambient NO2 levels were obtained from the Portuguese Environment Agency’s online database QualAr. Only monitoring stations that reported valid data for at least 75% of the time in a year were considered. The number of IHD mortality cases from 2011 to 2021 was sourced from Statistics Portugal. The burden of IHD attributed to NO2 exposure was estimated in YLL for the Portuguese population aged 25 years and older, categorized by five-years age groups, regions of mainland Portugal and sex, using the population attributable fraction (PAF). Results Between 2011 and 2021, mainland Portugal experienced a declining trend in NO2 mean levels, with occasional fluctuations. Regarding IHD YLL attributed to NO2 exposure, the same trend was followed with an overall decline over the study period. In total, 94,843.75 (95% CI 53,408.35-134,766.17) IHD YLL were attributed to NO2 exposure, with an estimated number of IHD YLLs higher for males than for females. Conclusions These findings underscore the significant impact of air pollution on human health. Despite an overall reduction in YLL across mainland Portugal, persistent health effects emphasize the need to reduce NO2 concentrations, with informed decision-making being crucial to mitigate these impacts and protect public health. Key messages • Ambient NO2 exposure significantly impacts ischemic heart disease mortality in Portugal. • These estimates underscore the necessity of well-informed decision-making to safeguard public health.