Our objectives in reviewing the initial experience of a hereditary hemorrhagic telangiectasia center of excellence (HHT COE) were to better understand the interventions being performed in the comprehensive care of these patients and to present the early data as a reference for other tertiary centers considering starting an HHT COE. We conducted a retrospective review of consecutive patients referred to our newly developed HHT COE for evaluation and treatment between May 2010 and June 2013. Clinical presentation, otolaryngologic treatments, and other operative interventions were analyzed. One hundred forty-four of the 198 patients (73%) evaluated at the HHT COE had definite HHT based on the Curaçao diagnostic criteria, with 20 additional patients possibly having HHT and undergoing further evaluation to confirm the diagnosis. Sixteen of the 31 patients (52%) referred to otolaryngology required intervention in the operating room for epistaxis. Seventy-two of the 164 (44%) patients with definite or possible HHT required other interventions for internal organ arteriovenous malformations (AVMs), with interventional radiology embolization of pulmonary AVMs being the most common procedure. An HHT COE is important in providing comprehensive care for patients with this rare disease, which has significant clinical sequelae. Having an HHT COE allows for early screening and subspecialty referral within a system of specialists experienced in preventing the morbidity and mortality associated with severe epistaxis and internal organ AVMs.