Objective To assess the efficacy and safety of hyperbaric oxygen treatment for patients with post-stroke depression. Methods Randomized controlled trials (RCTs) about hyperbaric oxygen treatment with placebo or open control in patients with post-stroke depression were comprehensively retrieved in PubMed (1966 to 2012.12), EMbase (1974 to 2012.12), EBSCO (1965 to 2012.12), CENTRAL (2012.11), CBM (1978 to 2012.12), CNKI (1980 to 2012.12), and VIP (1989 to 2012.12). References of the included articles were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the quality of the included studies. Then, meta-analysis was performed using RevMan 5.0. Results Twelve trials involving 822 patients were included, all of which were randomized non-placebo controlled trials. The results of meta-analysis of 12 trials (n=822) showed, the improvement of depression symptoms in the HBO group was better than that in the control group (MD=4.82, 95%CI 3.12 to 6.52). However, funnel plot showed that publication bias was large. After removing three trials for sensitive analysis, the results showed that the improvement of depression symptoms in the HBO group was still better than that in the control group (MD=3.91, 95%CI 3.35 to 4.47). Adverse events were reported in 2 trials, including dizziness, palpitation, mild earache, tinnitus, etc. However, no severe adverse events occurred. Conclusion Current evidence indicates that, HBO can effectively reduce the score of HAMD and no serious adverse reactions occurred. It’s necessary to further carry out high quality randomized controlled trials with large sample size due to limited quality and quantity of the included studies, so as to assess its effectiveness and safety.