Background <p>Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal multi-systemic vascular dysplasia caused by gene mutations that lead to recurrent epistaxis and other serious complications including mucocutaneous telangiectasias, gastrointestinal bleeding, and arteriovenous malformations. Treatment is limited to symptomatic relief with no approved standard therapy. Bevacizumab is a monoclonal antibody used primarily in treating metastatic malignancies and ophthalmology. Several studies have shown that bevacizumab is effective in the treatment of HHT-related epistaxis with a high safety profile.</p> Purpose <p>This systematic review and network meta-analysis aims to explore the efficacy and safety of bevacizumab in the treatment of HHT epistaxis.</p> Methods <p>A comprehensive literature search was done in many databases, including PubMed, Web of Science, Scopus, and the Cochrane Library. We conducted our network meta-analysis using R version 4.2.2 and R Studio version 2022.07.2. Dichotomous data was analyzed as risk ratio and 95% confidence interval and continuous data as mean difference and 95% confidence interval.</p> Results <p>We included four randomized clinical trials in our network meta-analysis. Different doses of bevacizumab failed to yield any statistically significant difference in reducing the epistaxis severity score, the number of epistaxis episodes, the duration of epistaxis, or improving hemoglobin levels compared to placebo or other comparators. The pooled effect sizes for all outcomes were homogenous.</p> Conclusion <p>Bevacizumab failed to show any significant difference compared to tranexamic acid, estriol, or placebo. These findings underscore the challenges in addressing HHT-related symptoms and highlight the ongoing need for innovative and more effective interventions.</p>