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OBJECTIVE: Assess the cost-effectiveness of a 16-week weight loss intervention (Weight-Wise) for low-income midlife women. METHOD: A randomized controlled trial conducted in North Carolina in 2007 tested a weight loss intervention among 143 women (40-64 years old, mean BMI=35.1 kg/m(2)). Women were randomized to one of two arms-special intervention (n=72) and a wait-listed control group (n=71). Effectiveness measures included changes in weight, systolic and diastolic blood pressure, total cholesterol, and HDL cholesterol. Cost-effectiveness measures calculated life years gained (LYG) from changes in weight, based on excess years life lost (YLL) algorithm. RESULTS: Intervention participants had statistically significant decreases in weight (kg) (-4.4 95% CI=-5.6, -3.2) and in systolic blood pressure (-6.2 mm Hg, 95% CI=-10.6, -1.7) compared to controls. Total cost of conducting Weight-Wise was $17,403, and the cost per participant in intervention group was $242. The incremental cost per life year gained (discounted) from a decrease in obesity was $1862. CONCLUSION: Our results suggest the Weight-Wise intervention may be a cost-effective approach to improving the health of low-income women.