Context: Despite implementation of the Affordable Care Act (ACA), as of 2015, about 25.8 million working-age Americans remained uninsured and vulnerable to premature death because of poor health care access. The ACA-mandated phasing out of disproportionate share hospital payments that supported charity care may aggravate care access for the residual uninsured. Objectives: To estimate excess deaths among the uninsured and the potential ACA impact on the basis of a recent cohort's mortality experience. We hypothesized a higher uninsured mortality risk than the available pre-2000 estimate because of worsening of care disparities owing to technology-driven advances in life-saving care. Design: We conducted a retrospective cohort study of the 1999 to 2002 National Health and Nutrition Examination Survey respondents observed through 2011. We estimated (a) weighted Cox proportionalmortality hazard of uninsuredworking-age adults adjusted for demographics, comorbidity, and lifestyle behaviors, (b) weighted mortality rates among the uninsured and insured within age and comorbidity strata, and (c) excess deaths because of uninsurance using the Institute ofMedicine methodology. Setting: Noninstitutionalized US population. Participants: Adults aged 20 to 64 years. Main Outcome Measure: Mortality. Results: Of 7274 study-eligible respondents, 20.6% were uninsured and 478 died during follow-up, for an adjusted uninsured mortality hazard ratio of 1.57 (95% confidence interval, 1.12-2.21) versus privately insured, translating to 48 529 excess deaths among the population aged 25 to 64 years in 2011 (7.8% of total deaths in this age group). The estimated proportion of excess deaths was 52% higher than the pre-2000 cohort study. The mortality disparity increased with age and comorbidity. Conclusions: Findings support our hypotheses, and indicate that post-ACA, a residual 4.7% excess mortality among working-age adults will continue, about 30 428 excess deaths annually. Restoration of disproportionate share hospital supports and continued advocacy for universal health care coverage are needed to reduce avoidable deaths.