Background: Functional dyspepsia (FD) is connected with abdominal pain and nausea, which leads to reduced quality of life, loss of productivity, and economic loss for patients. Itopride hydrochloride stimulates the gastrointestinal smooth muscles, thereby promoting gastric emptying, and has been shown to significantly improve symptoms in patients with FD without severe side effects. Itopride hydrochloride has been available in Vietnam for many years; however, the cost-effectiveness of the drug has not been established. The aim of this study is to estimate the cost-effectiveness of itopride hydrochloride for treatment of FD in Vietnam. Methods: A three-stage Markov model with the following health states: controlled FD, uncontrolled FD, and dead. FD was used to assess itopride over 10 years using 8-week cycles. From a broader Vietnamese societal perspective, input was retrieved from the literature and through local clinical experts. Output was reported as incremental cost-effectiveness ratio (ICER) per quality adjusted life years (QALY). A GDP/capita threshold (cost-effective: 1 × GDP = VND64.1M, cost-effective: 3 × GDP = VND192.2M) was used as the WHO and in Vietnam was used. One-way and probabilistic sensitivity analyses were performed. Results: Itopride hydrochloride resulted in additional 0.65 QALYs at an extra cost of VND29.1M. This resulted in an ICER of VND39.5M per QALY, which is lower than the threshold of VND192.2M. The one-sensitivity analyses showed that the ICER was sensitive to varying efficacy (ICER: VND24.8M to VND69.0M), cost of itopride (ICER: VND33.6M to VND45.4M), and the health utility values (ICER: VND35.9M to VND43.9M). More than 80% of the simulations in the probabilistic sensitivity analysis were cost-effective at the 1 × GDP (VND64.1M) threshold, and 91.3% were cost-effective at the 3 × GDP (VND192.2M) threshold. Conclusion: This study shows that itopride hydrochloride is the very cost-effective treatment for FD in Vietnam with the ICER (VND39.5M/QALY) being even lower than the 1 × GDP (VND64.1M) threshold.