ABSTRACT Aim To reassess the efficacy of hyperbaric oxygen (HBO) therapy for acute carbon monoxide (CO) poisoning through a systematic review and meta‐analysis, including a subgroup analysis of treatment pressures exceeding 2.5 atm absolute (ATA). Methods We conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) evaluating HBO therapy for acute CO poisoning. A literature search was performed in MEDLINE, CENTRAL, and Ichushi‐Web databases, focusing on RCTs published up to June 2024. Only adult patients (≥ 18 years) were included, and studies were screened following PRISMA guidelines. Data extraction and quality assessment were conducted by two independent reviewers using the Cochrane risk of bias tool and the GRADE approach. Statistical analysis used a random effects model, with outcomes expressed as odds ratios (OR) and 95% confidence intervals (CI). Results Six studies were included, and no significant benefit of HBO therapy was observed in terms of reducing mortality or improving neurological outcomes. The subgroup analysis of HBO at ≥ 2.5 ATA also showed no significant advantage over control treatments. Moderate to significant heterogeneity was found across included studies, and the quality of evidence was rated as low to very low. Conclusions The efficacy of HBO therapy, even at ≥ 2.5 ATA, for improving outcomes in acute CO poisoning remains unproven. Despite these findings, HBO therapy may still hold potential benefits that require further exploration. High‐quality, multicenter RCTs are necessary to better define its role in the treatment of CO poisoning. Trial Registration UMIN Clinical Trials Registry: UMIN000054641
Fujita et al. (Thu,) studied this question.