Objectives Epistaxis is the most frequent clinical manifestation of hereditary hemorrhagic telangiectasia (HHT). Several topical, systemic, and surgical treatments have been tried, but none have been completely effective. The aim of the present study is to evaluate whether a combined treatment sclerotherapy and topical therapy with propranolol 0.5% nasal formulation would reduce the epistaxis due to HHT and improve patient's quality of life. Methods An observational cross‐sectional study was carried out. The primary outcome measure was frequency and severity of epistaxis as measured by the epistaxis severity score (ESS) at baseline (4 weeks before therapy) and at least 4 weeks after the treatment was implemented. Quality of life was analyzed using EuroQol‐5D (EQ‐5D) scale and visual analogue (VAS) scale before and after treatment. Results A total of 38 consecutive patients subjected to the combined treatment were evaluated (mean age: 57.2 years, standard deviation [SD] = 13.9; 60.5% women). The mean time of treatment was 37.1 weeks (SD = 14.9). Combined therapy significantly reduces frequency and severity of epistaxis, with an ESS improvement of 5 points from 6.9 ± 2.6 to 1.9 ± 1.3 (P < 0.05); however, the EQ‐5D scale increased from 0.66 ± 0.27 to 0.93 ± 0.12 (P < 0.05). The difference in VAS means showed an increase from 44.6 ± 28.3 to 82.5 ± 12.5 (P < 0.05). The increases in quality of life are in line with the drop in ESS. Conclusion The study demonstrated that combined therapy (sclerotherapy and topical nasal propranolol) significantly reduced the epistaxis due to HHT and increased patients’ quality of life. Level of Evidence 2c Laryngoscope, 129:2216–2223, 2019