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We evaluated whether Nurse-Family Partnership might serve as a cost-effective social policy for improving health. Using data from studies of randomized controlled trials as well as real-world data, we conducted a Monte Carlo simulation to estimate cost-effectiveness of Nurse-Family Partnership in a hypothetical cohort of first-born children in the United States. Analyses were conducted in 2015. Were all new mothers eligible for Nurse-Family Partnership, the program would produce 0.11 QALYs (95% confidence interval [CI]=0.06, 0.17) at an additional cost of $1,021 (95% CI=-$2,831, $4,414) per nurse-visited child's lifetime relative to the comparison-group children or $14,642 (95% CI = Savings, $71,877) per QALY gained. However, if applied to high-risk mothers, it would generate 0.19 QALYs (95% CI = 0.09, 0.44) and a net benefit of $2,764 (95% CI =-$1,210, $7,092) per nurse-visited child. Nurse-Family Partnership should be considered as a policy investment, particularly in an era of investments in the social determinants of health.