IntroductionMedical financial hardship in the United States is a growing public health concern. This study aims to assess the south vs. non-south disparities in medical financial hardship among US adults of different generations – Boomers (born between 1946 and 1964), Generation X (born between 1965 and 1980), and the Millennials (born between 1981 and 1996) across periods pre- and post- Affordable Care Act (ACA).MethodsThis observational study utilizes data from multiple waves of the National Health Interview Survey (NHIS) split into three periods: pre–ACA (2011–2013), ii) post ACA (2015–2018), and iii) COVID-19 pandemic (2021–2022). Multivariable logistic regressions were fitted, separately for each generation in each period, to compare the extent of medical financial hardship among those from South to rest of the US, and Karlson-Holm-Breen (KHB) decomposition was applied to analyze whether there was a mediating impact of health insurance coverage.ResultsAdults living in the South were more likely to experience medical financial hardship in all three periods. Residing in the South was associated with 1.7 to 2.6% points (pp) higher probability of medical financial hardship among boomers, 1.8 to 4.0 pp among generation Xers, and 1.7 to 2.8 pp among millennials. The relationship was robust after accounting for chronic comorbidities, sociodemographic and socioeconomic attributes and was partially mediated through differences in health insurance coverage.ConclusionsThe problem of medical financial hardship has been deeply rooted in the South across generations, which was partly attributable to the regional differences in health insurance coverage.