Purpose: Oral branched-chain amino acids (BCAAs) may benefit patients with cirrhosis, especially those with hepatic encephalopathy (HE). We analyzed the cost-effectiveness of BCAAs in improving the prognosis of patients with HE. Materials and Methods: We compared the total costs and effectiveness of oral BCAA treatment (Scenario 1) versus no BCAA supplementation (Scenario 2) in a virtual cohort of 10000 patients who had experienced HE over a 5-year period. A nested Markov model consisting of four health states (remission, recurrence, stabilization after recurrence, and death) for decompensated cirrhosis was used. Effectiveness was estimated as the cumulative number of HE recurrences and deaths. Additionally, the number of life-years and quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were analyzed. Deterministic and probabilistic sensitivity analyses were also performed. Results: Oral BCAA treatment prevented 34% of HE recurrences and reduced the number of HE-related deaths by 18%. Although patients in the BCAA-treated group spent an additional 4086 USD on average compared with their counterparts in the non-treated group ($27088 vs. $23003), they experienced 0.34 more QALYs (2.77 vs. 2.43) over the 5-year period. The ICER for BCAA treatment was 12017 USD/QALY, indicating the high cost-effectiveness of the therapeutic option. Moreover, the sensitivity analyses showed that its economic feasibility was robust. With the willingness-to-pay threshold set at 1 GDP per capita, the probability of cost-effectiveness of BCAA treatment exceeded 80%. Conclusion: Oral BCAAs for HE prevention may contribute positively to both the clinical status of the patient and the national healthcare budget.