This study aimed to examine the cost-effectiveness of one-time standard endoscopic screening with Lugol’s iodine staining for esophageal cancer (EC) in China. A Markov decision analysis model with eleven states was built. Individuals aged 40 to 69?years were classified into six age groups in five-year intervals. Three different strategies were adopted for each cohort: (1) no screening; (2) one-time endoscopic screening with Lugol’s iodine staining with an annual follow-up for low-grade intraepithelial neoplasia (LGIN); and (3) one-time endoscopic screening with Lugol’s iodine staining without follow-up. Quality-adjusted life-years (QALYs) indicated the effectiveness of the model. The incremental cost-effectiveness ratio (ICER) was used as the evaluation indicator. Sensitivity analysis was performed to assess the robustness of the model. One-time screening with follow-up was the undominated strategy for individuals aged 40–44 and 45–49?years, which saved USD 10,942.57 and USD 6611.73 per QALY gained compared to nonscreening strategy. For those aged 50–69?years, the nonscreening scenarios were undominated. One-time screening without follow-up was the extended dominated strategy. Compared to screening strategies without follow-up, all the screening strategies with follow-up were more cost-effective, with the ICER increasing from 299.57 USD/QALY for individuals aged 40–44?years to 1617.72 USD/QALY for individuals aged 65–69?years. Probabilistic sensitivity analysis (PSA) supported the results of the base case analysis. One-time EC screening with follow-up targeting individuals aged 40–49?years was the most cost-effective strategy.
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