Background: Traumatic brain injury (TBI) is a leading cause of fatalities and disabilities in the public health domain, particularly in Thailand. Guidelines for TBI patients advise intracranial pressure monitoring (ICPm) for intensive care. However, information about the cost-effectiveness (CE) of ICPm in cases of severe TBI is lacking. This study assessed the CE of ICPm in severe TBI. Methods: This was a retrospective cohort economic evaluation study from the perspective of the healthcare system. Direct costs were sourced from electronic medical records, and quality-adjusted life years (QALY) for each individual were computed using multiple linear regression with standardization. Incremental costs, incremental QALY, and the incremental CE ratio (ICER) were estimated, and the bootstrap method with 1,000 iterations was used in uncertainty analysis. Results: The analysis included 821 individuals, with 4.1% undergoing intraparenchymal ICPm. The average cost of hospitalization was United States dollar ($)8,697.13 (±6,271.26) in both groups. The incremental cost and incremental QALY of the ICPm group compared with the non-ICPm group were $3,322.88 and –0.070, with the base-case ICER of $–47,504.08 per additional QALY. Results demonstrated that 0.007% of bootstrapped ICERs were below the willingness-to-pay (WTP) threshold of Thailand. Conclusions ICPm for severe TBI was not cost-effective compared with the WTP threshold of Thailand. Resource allocation for TBI prognosis requires further development of cost-effective treatment guidelines.