Limited therapeutic options remain for patients with refractory esophageal strictures who have failed through-the-scope (TTS) balloon dilation, incisional therapy, stent placement, or steroid injection. Application of Mitomycin C, a chemotherapeutic antibiotic agent, is believed to reduce the rate of re-stenosis via local inhibition of DNA synthesis and reduction of fibroblastic collagen formation. The primary aim of this study was to perform a systematic review and meta-analysis to investigate the efficacy and safety of Mitomycin C for patients with refractory esophageal strictures. Individualized search strategies were developed for PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception through October 2019 in accordance with PRISMA and MOOSE guidelines. This was a cumulative meta-analysis performed by calculating pooled proportions with rates estimated using random effects models. Only cases involving adult patients with esophageal strictures were included. Studies with <5 patients were excluded to minimize selection bias. Measured outcomes included pooled technical success rate, clinical success rate (defined as complete or partial improvement in dysphagia symptoms), Mitomycin C concentration and volume applied, number of applications required, procedure-associated adverse events, and need for repeat treatment. Heterogeneity was assessed with I2 statistics and publication bias by funnel plot using Egger and Begg tests. A total of 8 studies (n=101 patients; 37.5% male) were included in this meta-analysis. Both topical application with cotton pledgets and injection of Mitocmycin C were utilized. Mean age of included patients was 65.22 ±5.11 years with a study follow-up period of 11.68 ±10.16 months. Pooled technical success was 95.82% (95% CI, 89.35 to 98.43); I2=0.00 with a clinical success of 95.34% [(95% CI, 87.47 to 98.36); I2=0.00]. Complete response was achieved in 58.47% [(95% CI, 25.36 to 85.37); I2=65.56] of patients a. Limited sustained response and repeat intervention was needed in 43.99% [(95% CI, 19.60 to 71.68); I2=53.37] of patients. Most studies utilized a 0.4 mg/mL concentration of Mitomycin C with an average of 7.21 mL used. There was a mean of 3.25 (range 1 to 6) applications performed. Procedure-associated adverse events occurred in 14.09% [(95% CI, 7.88 to 23.92); I2=0.00] with most classified as mild-to-moderate based upon ASGE lexicon. Use of Mitomycin C appears to be a safe and effective treatment for esophageal strictures refractory to conventional methods of therapy. Although repeat intervention is commonly required, a majority of patients with severe, refractory strictures experience improvement in dysphagia symptoms. Future studies should investigate the cost-effectiveness, optimal dose, and delivery of this technique.