The purpose of this study was to describe the results of Nd:YAG laser application in hereditary hemorrhagic telangiectasia (HHT) patients and to measure the Health-Related Quality of Life (HR-QoL) in patients with HHT before and after Nd:YAG laser application in a prospective, clinical trial at a university hospital. Twenty-seven consecutive patients with HHT and mild to moderate degrees of epistaxis were followed-up for 2 years after Nd:YAG laser treatments. Recurrence of epistaxis after Nd:YAG laser application and measurement of HR-QoL using the International Quality of Life Assessment questionnaire, version 1.1 (IQOLA 1.1), was found. Eight patients (30%) received only one Nd:YAG laser treatment, 15 (56%) had a recurrence and received a second treatment and 4 (14%) had two recurrences and received three Nd:YAG laser treatments. HR-QoL was improved 2 years after the first Nd:YAG laser application in both its Physical Health Dimension (47.5+/-2.9 vs. 38.1+/-2.3 before treatment, P <0.05) and Mental Health Dimension (45.1+/-2.7 vs. 39.6+/-2.4 before treatment, P <0.05). Although no curative treatment for HHT exists, Nd:YAG laser treatment seems to constitute a simple and efficient method of epistaxis control, resulting in a significant improvement in quality of life.