Context: Regional poverty is associated with reduced access to health care. Whether this relationship is equally strong in both rural and urban settings or is affected by the contextual and individual-level characteristics that distinguish these areas, is unclear. Purpose: Compare the association between regional poverty with self-reported unmet need, a marker of health care access, by rural/urban setting. Methods: Multilevel, cross-sectional analysis of a state-representative sample of 39,953 adults stratified by rural/urban status, linked at the county level to data describing contextual characteristics. Weighted random intercept models examined the independent association of regional poverty with unmet needs, controlling for a range of contextual and individual-level characteristics. Findings: The unadjusted association between regional poverty levels and unmet needs was similar in both rural (OR = 1.06 [95% CI, 1.04-1.08]) and urban (OR = 1.03 [1.02-1.05]) settings. Adjusting for other contextual characteristics increased the size of the association in both rural (OR = 1.11 [1.04-1.19]) and urban (OR = 1.11 [1.05-1.18]) settings. Further adjustment for individual characteristics had little additional effect in rural (OR = 1.10 [1.00-1.20]) or urban (OR = 1.11 [1.01-1.22]) settings. Conclusions: To better meet the health care needs of all Americans, health care systems in areas with high regional poverty should acknowledge the relationship between poverty and unmet health care needs. Investments, or other interventions, that reduce regional poverty may be useful strategies for improving health through better access to health care.