We studied the health of low-income US women affected by the largest social policy change in recent US history: the 1996 welfare reforms. Using the Behavioral Risk Factor Surveillance System (1993-2012), we performed 2 types of analysis. First, we used difference-in-difference-in-differences analyses to estimate associations between welfare reforms and health outcomes among the most affected women (single mothers aged 18-64 years in 1997; n = 219,469) compared with less affected women (married mothers, single nonmothers, and married nonmothers of the same age range in 1997; n = 2,422,265). We also used a synthetic control approach in which we constructed a more ideal control group for single mothers by weighting outcomes among the less affected groups to match pre-reform outcomes among single mothers. In both specifications, the group most affected by welfare reforms (single mothers) experienced worse health outcomes than comparison groups less affected by the reforms. For example, the reforms were associated with at least a 4.0-percentage-point increase in binge drinking (95% confidence interval: 0.9, 7.0) and a 2.4-percentage-point decrease in the probability of being able to afford medical care (95% confidence interval: 0.1, 4.8) after controlling for age, educational level, and health care insurance status. Although the reforms were applauded for reducing welfare dependency, they may have adversely affected health.