Work requirements are a controversial feature of US safety-net programs, with some policymakers seeking to expand their use. Little is known about the demographic, clinical, and socioeconomic characteristics of individuals most likely to be negatively impacted by work requirements. To examine the association between work requirements and safety-net program enrollment. This cohort study included Medicaid and Supplemental Nutrition Assistance Program (SNAP) enrollees in Connecticut. The impact of SNAP work requirements for able-bodied adults without dependents-the target population-was estimated using a triple-differences research design comparing outcomes before and after the policy (first difference) in affected and exempted towns (second difference) between the targeted population and untargeted parents and caregivers (third difference). SNAP and Medicaid enrollment trends were assessed for a 24-month period, and the characteristics of individuals most likely to lose coverage were examined. Data were collected from August 2015 to April 2018, and data were analyzed from August 2022 to September 2024. The reintroduction of SNAP work requirements in 2016. Proportion of enrollees disenrolled from SNAP and Medicaid. Of 81 888 Medicaid enrollees in Connecticut, 46 872 (57.2%) were female, and the mean (SD) age was 36.6 (7.0) years. Of these, 38 344 were able-bodied adults without dependents, of which 19 172 were exposed to SNAP work requirements, and 43 544 were parents or caregivers exempted from SNAP work requirements. SNAP coverage declined 5.9 percentage points (95% CI, 5.1-6.7), or 25%, following work requirements. There were no statistically significant changes in Medicaid coverage (0.2 percentage points; 95% CI, -1.4 to 1.0). Work requirements disproportionately affected individuals with more chronic illnesses, targeted beneficiaries who were older, and beneficiaries with lower incomes. Individuals with diabetes were 5 percentage points (95% CI, 0.8-9.3), or 91%, likelier to lose SNAP coverage than those with no chronic conditions; older SNAP beneficiaries (aged 40 to 49 years) with multiple comorbidities were 7.3 percentage points (95% CI, 4.3-11.3), or 553%, likelier to disenroll than younger beneficiaries (aged 25 to 29 years) without chronic conditions; and households with the lowest incomes were 18.6 percentage points (95% CI, 11.8-25.4), or 204%, likelier to lose coverage than the highest income SNAP beneficiaries. In this cohort study, SNAP work requirements led to substantial reductions in SNAP coverage, especially for the most clinically and socioeconomically vulnerable. Work requirements had little effect on Medicaid coverage, suggesting they did not lead to sufficient increases in employment to transition beneficiaries off the broader safety net.