ObjectivesTo assess the cost-effectiveness of an opioid abuse–prevention program embedded in the Narcotics Information Management System (“the Network System to Prevent Doctor-Shopping for Narcotics”) in South Korea. MethodsUsing a Markov model with a 1-year cycle length and 30-year time horizon, we estimated the incremental cost-utility ratio (ICUR) of implementing an opioid abuse–prevention program in patients prescribed outpatient opioids from a Korean healthcare payer’s perspective. The model has 6 health states: no opioid use, therapeutic opioid use, opioid abuse, overdose, overdose death, and all-cause death. Patient characteristics, healthcare costs, and transition probabilities were estimated from national population-based data and published literature. Age- and sex-specific utilities of the general Korean population were used for the no-use state, whereas the other health-state utilities were obtained from published studies. Costs (in 2019 US dollars) included the expenses of the program, opioids, and overdoses. An annual 5% discount rate was applied to the costs and quality-adjusted life-years (QALYs). Parameter uncertainties were explored via deterministic and probabilistic sensitivity analyses. ResultsThe program was associated with 2.27 fewer overdoses per 100 000 person-years, with an ICUR of $227/QALY. The ICURs were generally robust to parameter changes, although the program’s effect on abuse reduction was the most influential parameter. Probabilistic sensitivity analysis showed that the program reached a 100% probability of cost-effectiveness at a willingness-to-pay threshold of $900/QALY. ConclusionsThe opioid abuse–prevention program appears to be cost-effective in South Korea. Mandatory use of the program should be considered to maximize clinical and economic benefits of the program.