PM2.5 pollution had been a global public health problem, leading risk factor for DisabilityAdjusted Life Years in 2019. In Vietnam, air pollution has been increasing rapidly in urban areas, resulting in adverse impacts on public health. This study aims to estimate the health burden attributed to ambient PM2.5 pollution and cost loss in 2016–2019 period in Hanoi and Ho Chi Minh City. Exposure-response function was used to estimate the health impacts and statistical life (VSL), cost of illness (COI), and human capital approach (AHC) were applied for external cost estimation. The results showed that the predominance of the respiratory diseases was in children and cardiovascular mortality diseases prevailed in adults. Female was more affected by cardiovascular premature deaths and male was more affected by lung cancer and respiratory fatalities. In 2016- 2019 period, the average annual cost for the reduction of health effects was equivalent to 0.09% and 0.04% of GDP in Hanoi and Ho Chi Minh City, respectively. The adverse health caused by PM2.5 exposures should not be neglected in Vietnam.