Purpose <p>This simulation-based cost-effectiveness analysis evaluates various sedation regimens for pediatric magnetic resonance imaging (MRI) in Japan.</p> Methods <p>A decision tree model was developed for children aged 3&#xa0;years with ASA-PS class I/II to compare four sedation regimens: oral triclofos sodium, IV midazolam, IV dexmedetomidine, and IV propofol. The primary outcome was averted sedation failure (aSF). Cost-effectiveness was assessed using the incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses, including Monte Carlo simulations and cost-effectiveness acceptability curves (CEACs), were performed. A 0% discount rate was applied. Our systematic literature search determined success rates for each sedation or general anesthesia regimen.</p> Results <p>The cost-effectiveness plane demonstrated the efficiency frontier connecting triclofos sodium, propofol, and general anesthesia. Compared to oral triclofos sodium, propofol had an ICER of $3214.06 per additional aSF, which was more favorable than dexmedetomidine (ICER: −$9222.85). Sensitivity analysis showed that ICER values were most sensitive to the success rates of each sedation regimen, followed by the reimbursement rate for anesthesiologist-administered sedation. CEACs confirmed that triclofos sodium and propofol were the most favorable, while midazolam and general anesthesia were less favorable. The probability of cost-effectiveness for propofol varied from 0 to 51.6%, and for triclofos sodium, it ranged from 100 to 38.9%.</p> Conclusion <p>Propofol sedation administered by anesthesiologists demonstrated superior cost-effectiveness compared to dexmedetomidine and midazolam sedation administered by non-anesthesiologists, primarily due to higher success rate and lower reimbursement rate for sedation procedures by anesthesiologists. Increasing reimbursement for anesthesiologist-administered sedation may be justifiable, though further real-world validation is needed.</p>