Background Studies evaluating health-related quality of life (HRQOL) in patients with hereditary hemorrhagic telangiectasia (HHT) have expanded rapidly in the past decade. These studies have evaluated QOL aspects ranging from the general QOL for patients living with HHT to intervention-specific outcomes. However, few tools have been fully validated across the spectrum of disease manifestations and interventions in HHT. Objective In this scoping review, we aim to map the literature on HHT-QOL metrics, identify gaps, inform future QOL research, and facilitate future metric development. Methods We analyzed articles in English that assessed at least 1 measure of general HRQOL, including physical health, mental health, social health, or intervention-specific QOL in patients with HHT. Searches across 2 bibliographic databases (PubMed and Scopus) yielded 186 articles after duplicates were removed. Sixty-three studies met eligibility criteria: 22 prospective studies (34.9%), 20 retrospective studies (31.7%), 12 cross-sectional studies (17.5%), 6 randomized controlled trials or secondary analyses of a randomized controlled trials (9.5%), 2 qualitative studies (3.2%), and 1 case-control study (1.6%). Two additional studies—1 prospective and 1 cross-sectional study—were identified at the October 2022 14th International HHT Conference and included, making a total of 65 studies. Results The 65 eligible studies used 30 QOL instruments. Twenty studies characterized baseline HRQOL, and 45 studies evaluated QOL before and after treatment. Of those 45 studies, 37 evaluated HRQOL before and after therapies targeting epistaxis and nasal symptoms, 4 targeted therapies for liver arteriovenous malformations and high-output heart failure, 3 evaluated therapies for both epistaxis and gastrointestinal bleeding, and 1 evaluated treatment targeting gastrointestinal bleeding alone. Conclusions Comparison of results across studies remains challenging given the heterogeneity in outcomes measures. Further development of HHT-specific patient-reported outcomes instruments that capture the global illness experience of HHT is needed.