Importance: Changes in insurance coverage after the Affordable Care Act (ACA) among non-elderly adults with self-reported chronic conditions across income categories have not been described. Objective: To examine changes in insurance coverage after the ACA among non-elderly adults with chronic conditions across income categories, by geographic region. Design: We compared self-reported access to health insurance pre-ACA (2010-2013) and post-ACA (2014-2017) for individuals 18-64 years of age with ≥ 2 chronic conditions, including hypertension, heart disease/stroke, emphysema, diabetes, asthma, cancer, and arthritis, across regions using a logistic regression approach, adjusted for covariates. We also assessed U.S. Census regional differences in insurance coverage post-ACA using modified Poisson regression models with robust variance and calculated the risk ratio (RR) of being uninsured by region, with the Northeast as the reference category. Within each region, we then examined changes in insurance coverage by income level among non-elderly individuals with any chronic condition. Setting: 2010–2017 household component of the nationally representative Medical Expenditure Panel Survey (MEPS). Participants: All members of surveyed households during five interviews over a two-year period. Intervention: Start of insurance coverage expansion under the ACA. Main outcomes: Health insurance status. Results: On average nationwide, non-elderly adults with self-reported chronic conditions experienced increased insurance coverage associated with the ACA (diabetes: +6.41%, high-blood pressure: +6.09%, heart disease: +6.50%, asthma: +6.37%, arthritis: +6.77%, and ≥ 2 chronic conditions: +6.39%). Individuals in the West region reported the largest increases (diabetes +9.71%, high blood pressure +8.10%, and heart disease/stroke +8.83 %, asthma +9.10%, arthritis +8.39%, and ≥ 2 chronic conditions +8.58). In contrast, individuals in the South region reported smaller increases in insurance coverage post-ACA among those with diabetes, heart disease/stroke, and asthma compared to the Midwest and West. The Northeast region, which had the highest levels of insurance coverage pre-ACA, exhibited the smallest increase in reported coverage post-ACA. Reported insurance coverage improved across all regions for adults with any chronic condition across income levels, most notably for very low- and low-income individuals. A further cross-sectional comparison after the ACA demonstrated important residual differences in insurance coverage, despite the gains in all regions. When compared to the Northeast, adults with any self-reported chronic conditions living in the South were more likely to report no insurance coverage (diabetes: RR 1.99, p-value <0.001, high blood pressure: RR 2.02, p-value <0.001, heart diseases/stroke: RR 2.55, p-value <0.001, asthma RR 2.21, p-value <0.001, arthritis: RR 2.25, p-value <0.001), and ≥ 2 chronic condition (RR 2.29, p-value <0.001). Conclusion and relevance: The ACA was associated with meaningful increases in insurance coverage for adults with any self-reported chronic condition in all US regions, most notably in the West region and among those with lower incomes, suggesting a nation-wide trend to improved access to health insurance following implementation. However, intra-regional comparisons after ACA implementation showed important differences. Individuals with ≥2 chronic conditions in the South were 2.29 times less likely to have insurance coverage in comparison to their peers in the Northeast. Though the post-ACA improvements in reported access to health insurance coverage affected all US regions, the reported experience of those with multiple chronic conditions in the South point to continued barriers for those most likely to benefit from access to health insurance coverage. Medicaid expansion in the South would likely result in increased insurance coverage for individuals with chronic conditions and improve health care outcomes. [ABSTRACT FROM AUTHOR]