BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, causes recurrent mucous membrane hemorrhage, especially epistaxis. In this systematic review, we discuss the efficacies of the three most common laser photocoagulation treatments for HHT-related epistaxis. STUDY DESIGN/MATERIALS AND METHODS: A systematic literature search was conducted in PubMed and MEDLINE from database inception to March 2019. Studies reporting epistaxis outcomes following argon, neodymium-doped yttrium aluminum garnet (Nd:YAG), and diode laser photocoagulation for HHT were included. χ2 and Barnards exact tests were utilized to detect differences in reduced epistaxis frequency and intensity rates. RESULTS: Fifteen out of 157 published studies met our eligibility criteria, spanning a collective 362 patients. Argon, Nd:YAG, and diode laser therapy reduced epistaxis frequency in 90.4%, 88.9%, and 71.1% of patients, respectively, and reduced epistaxis intensity in 87.8%, 87.2%, and 71.1% of patients, respectively. Diode laser photocoagulation significantly underperformed in both outcome measurements when compared with argon (frequency: P = 0.005; intensity: P = 0.034) and Nd:YAG (frequency: P = 0.012; intensity: P = 0.041). There was no significant difference between argon and Nd:YAG in reducing HHT epistaxis frequency (P = 0.434) or intensity (P = 0.969). Categorizing HHT patients by clinical severity demonstrated a higher rate of improvement in the mild-moderate group compared with the severe group in both argon (P < 0.001) and Nd:YAG (P < 0.001) therapeutic methods. While no significant differences were found in rates of improved epistaxis outcomes between argon and Nd:YAG in mild-moderate HHT patients (frequency: P = 0.061; intensity: P = 0.061), Nd:YAG demonstrated greater rates of reduction in epistaxis frequency (P = 0.040) and intensity (P = 0.028) than argon among severe HHT patients. CONCLUSIONS: HHT is a lifelong disease, plaguing patients with debilitating epistaxis. Intranasal laser photocoagulation of telangiectasias using argon or Nd:YAG laser therapy can yield improved epistaxis outcomes compared with diode laser photocoagulation. In severe cases of HHT, Nd:YAG laser therapy provides greater improvements in epistaxis outcomes than argon photocoagulation. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.