Context: Uninsured adults have less access to recommended care, receive poorer quality of care, and experience worse health outcomes than insured adults do. The potential health benefits of expanding insurance coverage for these adults may provide a strong rationale for reform. However, evidence of the adverse health effects of uninsurance has been largely based on observational studies with designs that do not support causal conclusions. Although recent research using more rigorous methods may offer a better understanding of this important subject, it has not been comprehensively reviewed. Methods: The clinical and economic literature since 2002 was systematically searched. New research contributions were reviewed and evaluated based on their methodological strength. Because the effectiveness of medical care varies considerably by clinical risk and across conditions, the consistency of study findings with clinical expectations was considered in their interpretation. Updated conclusions were formulated from the current body of research. Findings: The quality of research has improved significantly, as investigators have employed quasi-experimental designs with increasing frequency to address limitations of earlier research. Recent studies have found consistently positive and often significant effects of health insurance coverage on health across a range of outcomes. In particular, significant benefits of coverage have now been robustly demonstrated for adults with acute or chronic conditions for which there are effective treatments. Conclusions: Based on the evidence to date, the health consequences of uninsurance are real, vary in magnitude in a clinically consistent manner, strengthen the argument for universal coverage in the United States, and underscore the importance of evidence-based determinations in providing health care to a diverse population of adults.