Endoscopic eradication therapy using radiofrequency ablation (RFA) is considered an acceptable alternative to surveillance monitoring for Barrett's esophagus with low-grade dysplasia (LGD). This study aimed to estimate whether RFA for LGD is cost-effective and to determine which factors influence cost-effectiveness. A Markov model was developed to estimate the incremental cost per quality-adjusted life year (QALY) gained for RFA compared with endoscopic surveillance. An Australian longitudinal cohort study (PROBE-NET) provides the basis of the model. Replacing surveillance with RFA yields 10 fewer cases of HGD and 9 fewer esophageal adenocarcinoma (EAC)-related deaths per 1000 patients' treatment, given on average 0.192 QALYs at an additional cost of AU$9211 (€5689; US$6262) per patient (incremental cost-effectiveness ratio AU$47,815 per QALY). The model is sensitive to the rate of EAC from LGD health state, the utility values, and the number of RFA sessions. Hence, the incremental benefit ranges from 0.080 QALYs to 0.198 QALYs leading to uncertainty in the cost-effectiveness estimates. When the cancerous progression rate of LGD falls <0.47% per annum, the cost-effectiveness of RFA becomes questionable. RFA treatment of LGD provides significantly better clinical outcomes than surveillance. The additional cost of RFA is acceptable if the LGD to EAC rate is >0.47% per annum and no more than three RFA treatment sessions are provided. Accurate estimates of the risk of developing EAC in patients with LGD are needed to validate the analyses.