INTRODUCTION: Smoking is the leading preventable cause of death and disability in the United States. A 2019 randomized controlled trial found e-cigarettes are more effective than nicotine replacement therapy (NRT) in achieving abstinence when both are combined with behavioral counseling. Few cost-effectiveness studies have been performed regarding e-cigarettes as an adjunct to cessation efforts, and none in a U.S. context. This study evaluated the cost-effectiveness of e-cigarettes compared to NRT, both with counseling, and as cessation aids for Medicaid smokers in California. AIMS AND METHODS: A cost-effectiveness analysis from a U.S. societal perspective comparing e-cigarettes with NRT was constructed. Using a lifetime horizon, smokers were followed to different health states to their expected lifespan. Costs were expressed in 2020 U.S. dollars and health outcomes in quality-adjusted life years (QALY). All costs and outcomes were discounted at a 3% annual rate and model findings were assessed with a series of sensitivity analyses. RESULTS: Using U.S. willingness-to-pay thresholds, e-cigarettes were more cost-effective than NRT, with an incremental cost-effectiveness ratio of 1 454 per additional QALY gained over smokers' lifetimes. Results were sensitive to smokers' healthcare costs, model start ages, discount rates, and QALY weights. CONCLUSIONS: E-cigarettes used as a cessation treatment by smokers are more cost-effective relative to NRT. However, e-cigarettes as a treatment are currently unapproved by the Food and Drug Administration (FDA). Despite the lack of FDA approval, e-cigarettes are a popular choice among smokers trying to quit. Policymakers should consider whether providing financial support for e-cigarettes as a harm reduction strategy is worth pursuing. IMPLICATIONS: As e-cigarettes grow in popularity and are an increasingly preferred choice of smoking cessation aid among smokers attempting to quit, it is important to examine the inclusion of these products in tobacco policy, research, and practice. Several countries have now adopted or are in the process of adopting e-cigarettes as a medically licensed and regulated smoking cessation aid. Future smoking cessation strategies by U.S. policymakers may consider the adoption of e-cigarettes as a cost-effective harm reduction tool for use by current smokers seeking to quit.