Objectives. To evaluate the effects of a comprehensive traffic safety policy-New York City's (NYC's) 2014 Vision Zero-on the health of Medicaid enrollees. Methods. We conducted difference-in-differences analyses using individual-level New York Medicaid data to measure traffic injuries and expenditures from 2009 to 2021, comparing NYC to surrounding counties without traffic reforms (n = 65 585 568 person-years). Results. After Vision Zero, injury rates among NYC Medicaid enrollees diverged from those of surrounding counties, with a net impact of 77.5 fewer injuries per 100 000 person-years annually (95% confidence interval = -97.4, -57.6). We observed marked reductions in severe injuries (brain injury, hospitalizations) and savings of $90.8 million in Medicaid expenditures over the first 5 years. Effects were largest among Black residents. Impacts were reversed during the COVID-19 period. Conclusions. Vision Zero resulted in substantial protection for socioeconomically disadvantaged populations known to face heightened risk of injury, but the policy's effectiveness decreased during the pandemic period. Public Health Implications. Many cities have recently launched Vision Zero policies and others plan to do so. This research adds to the evidence on how and in what circumstances comprehensive traffic policies protect public health. (Am J Public Health. 2024;114(6):633-641. https://doi.org/10.2105/AJPH.2024.307617).