Data on whether the carbon dioxide (CO 2 ) laser is useful for treatment of genitourinary syndrome of menopause (GSM) are inconsistent. This meta-analysis evaluated the benefits and safety of CO 2 laser compared with sham treatment of GSM. A relevant literature search of Europe PMC, MEDLINE, Scopus, and ClinicalTrials.gov databases using specific keywords was conducted. The results of continuous variables were pooled into the standardized mean difference (SMD), whereas dichotomous variables were pooled into odds ratio with 95% confidence intervals (95% CI) using random-effects models. A funnel plot was used to assess for the presence of publication bias. A total of six randomized clinical trials were included. Pooled analysis revealed that CO 2 laser therapy was associated with a higher reduction in the Vaginal Assessment Scale (SMD, -0.81 [95% CI, -1.59 to -0.04]; P = 0.04; I2 = 88%) and Urinary Distress Inventory short form (SMD, -0.45 [95% CI, -0.84 to -0.06]; P = 0.02; I2 = 0%), and greater patient satisfaction rate (odds ratio, 5.46 [95% CI, 2.23 to 13.37]; P = 0.0002; I2 = 0%) when compared with sham-only treatment. Meanwhile, the Female Sexual Function Index, Vaginal Health Index, and Patient Global Impression Improvement did not differ significantly between groups. Adverse events were only mild with no serious adverse events reported. CO 2 laser therapy may improve the overall treatment of GSM with a relatively good safety profile. However, further randomized clinical trials with larger sample sizes are still needed to confirm the results of this study.