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Systematically review and critically evaluate all available published data on the use of topical mitomycin C (MMC) as an adjunctive in airway surgery.Published studies indexed in MEDLINE, EMBASE, or Cochrane databases. Inclusion criteria were English language, sample size greater than five, and publication of data applicable to the analysis of topical MMC and airway surgery outcomes.Evidence tables were compiled to include sample size, study design, and evidence level. Summary statistics, random-effects modeling, and subgroup analysis were performed.Twenty manuscripts (eight human, 12 animal) met the inclusion criteria. Seven of eight (87.5%) of the human studies and eight of 12 (66%) animal studies concluded topical MMC was beneficial to airway surgical outcomes. Eleven of twelve animal studies included randomization and a control group, compared with only two of eight human studies. Random-effects modeling of human studies (k=7) indicated that 81.4 percent (95% CI, 72.0%-90.9%; P < 0.001) of patients had improved outcomes attributable to MMC. Random-effects modeling of animal data included modeling of change in airway diameter (Hedge's G = −0.03; 95% CI, −0.66-0.60; P = 0.924) and the change in histologic measures (Hedge's G = 1.26; 95% CI, 0.596-1.92; P < 0.001) in MMC-treated animals vs controls.The majority of the published literature individually suggests the use of topical MMC improves airway surgery outcomes. However, heterogeneity within the clinical studies, the lack of controlled data, and the lack of significance in the pooled animal data (other than histologic outcomes) suggest that the utility of MMC is still undetermined.