<h3>Purpose/Objective(s)</h3> To describe the scope of patient-reported instruments used in clinical trials to assess health related quality-of-life (HRQoL) outcomes following treatment of head and neck cancer. <h3>Materials/Methods</h3> A systematic review was conducted. A query was performed on ClinicalTrials.gov for all completed and ongoing clinical trials between May 2011 and May 2021 that include patients with head and neck cancer and contain one of the following search terms: patient-reported outcomes, functional outcomes, or quality-of-life. Trials that did not list a specific patient-reported HRQoL instrument were excluded. Data collected included patient demographics, study status, study type, length of follow-up, instruments used, and whether HRQoL was a primary or secondary study endpoint. Instruments were classified as global or domain specific. <h3>Results</h3> 272 clinical trials met the inclusion criteria. The median number of patients enrolled was 74 (IQR: 44-115.5), and 85.3% of studies were interventional by design. The median length of HRQoL follow-up was 12 months (IQR: 3-24). Patient-reported HRQoL measures were considered a primary endpoint in 34.6% of studies. A total of 116 different HRQoL instruments were used. 65.4% reported using more than one instrument with a maximum of 10 instruments used in one study. The 5 most used global HRQoL instruments were the EORTC QLQ-C30 with the Head and Neck module (41% of trials using a global instrument), FACT-HN (19%), EQ-5D-5L(10%), UWQoL (7%) and MDASI-HN (7%). Domains not covered by any of the 5 most common global instruments but for which domain-specific instruments were found in the literature include lymphedema, skin, and stress. The most used swallowing-specific instruments were the MDADI (71%) and EAT-10 (17%). The most used pain-specific instruments were the Visual Analogue Scale (60%) and the Brief Pain Inventory (20%). The most used instrument for xerostomia was the University of Michigan Xerostomia Questionnaire (57%). The Hospital Anxiety and Depression Scale (48%) and Percieved Stress Scale (22%) were the most used instruments for mood and stress, respectively. <h3>Conclusion</h3> No universal standards currently exist for reporting HRQoL in head and neck cancer, and a wide range of global and domain specific tools are employed in clinical trials for assessing patient-reported outcomes. Clinicians should consider the comprehensiveness of each tool, its prevalence in the literature, and likelihood of patient completion when selecting the most appropriate instrument for clinical use.