Background Exposure to air pollution, a leading contributor to the global burden of disease, can cause economic losses. Driven by clean air policies, the air quality in China, one of the most polluted countries, has improved rapidly since 2013. This has enabled a unique, quasi-experiment to assess the economic impact of air pollution empirically. Methods and findings Using a series of nation-scale longitudinal surveys in 2011, 2013, and 2015, we first examined the questionnaire-based medical expenditure changes before and after the policy intervention for air pollution. Using a state-of-the-art estimator of the historical concentration of particulate matters with diameter less than 2.5 μm (particulate matter (PM)_2.5), we further quantified the association between household medical expenditure and PM_2.5 using mixed-effect models of the repeated measurements from 26,511 households in 126 cities. Regression models suggest a robust linear association between reduced PM_2.5 and saved medical expenditures, since the association did not vary significantly across models with different covariate adjustments, subregions, or subpopulations. Each 10 μg/m³ reduction in PM_2.5 was associated with a saving of 251.6 (95% CI: 30.8, 472.3; p-value = 0.026) Yuan in per capita annual medical expenditure. However, due to limitations in data quality (e.g., self-reported expenditures), and imperfect control for unmeasured confounders or impact from concurrent healthcare reform in China, the causality underlying our findings should be further confirmed or refuted. Conclusion In this study, we observed that compared with the PM_2.5 reduction in 2013, the PM_2.5 reduction in 2017 was associated with a saving of 552 (95% CI: 68, 1036) Yuan / (person × year), or approximately 736 billion Yuan (equivalent to 111 billion US dollar) per year nationally, which is equivalent to approximately 1% of the national gross domestic product of China.