Introduction: The US has required chain food establishments-including supermarkets-to display calorie labels on prepared (i.e., ready-to-eat) foods since 2018. Implementation of this supermarket calorie labeling policy reduced purchases of prepared foods from supermarkets, but it remains unknown whether the policy is cost-effective., Methods: In 2023-2024, this study applied the Childhood Obesity Intervention Cost-Effectiveness Study (CHOICES) microsimulation model to estimate the effects of the supermarket calorie labeling policy on health, costs, and cost-effectiveness over 10 years (2018-2027) for the US population. The model projected benefits overall and among racial, ethnic, and income subgroups. Sensitivity analyses varied assumptions about the extent to which consumers replace calorie reductions from prepared foods with calories from other sources (i.e., caloric compensation)., Results: From 2018-2027, the supermarket calorie labeling policy was projected to save $348 million in healthcare costs (95% Uncertainty Interval [UI]: $263-426 million), prevent 21,700 cases of obesity (95% UI: 18,200-25,400), including 3,890 cases of childhood obesity (95% UI: 2,680-5,120), and lead to 15,100 quality-adjusted life years (QALYs) gained across the US population (95% UI: 10,900-20,500). The policy was projected to prevent cases of obesity and childhood obesity across all racial, ethnic, and income groups. The policy was projected to be cost-saving when assuming low and moderate caloric compensation and cost-effective when assuming very high caloric compensation., Conclusions: A policy requiring calorie labels on prepared foods in supermarkets was projected to be cost-saving or cost-effective and lead to reductions in obesity across all racial, ethnic, and income groups., Competing Interests: Declaration of competing Interest No financial disclosures have been reported by the authors of this paper., (Copyright © 2024. Published by Elsevier Inc.)