Simple SummaryFollowing completion of chemotherapy and radiation for the treatment of head and neck cancer, a PET/CT scan is typically obtained 3 months later to assess how well the patient responded to treatment. The results of this PET/CT are often difficult to interpret because radiation can cause inflammation around the area being treated that can take months to resolve. We looked at 57 patients who had a repeat PET/CT scan performed after initial post-treatment imaging was unclear to examine whether this was helpful in determining whether these patients require further testing. Among this group, 48% of patients converted to having a complete response to treatment and none went on to develop treatment failure. Based on our findings, repeat PET/CT imaging can provide valuable information for head and neck cancer patients that can reduce the incidence of unnecessary biopsies and surgeries.Despite waiting 13 weeks to perform a PET/CT scan after completion of chemoradiation for head and neck squamous cell carcinoma (HNSCC), equivocal findings are often found that make assessing treatment response difficult. This retrospective study examines the utility of a repeat PET/CT scan in HNSCC patients following an incomplete response on initial post-treatment imaging. For this cohort of 350 patients, initial PET/CT was performed 13 weeks after completion of treatment. For select patients with an incomplete response, repeat PET/CT was performed a median of 91 days later. Primary endpoints were conversion rate to complete response (CR) and the predictive values of repeat PET/CT imaging. Of 179 patients who did not have an initial complete response, 57 (32%) received a repeat PET/CT scan. Among these patients, 26 of 57 (48%) had a CR on repeat PET/CT. In patients with CR conversion, there were no cases of disease relapse. The sensitivity, specificity, PPV, and NPV for the repeat PET/CT for locoregional disease were 100%, 59%, 42%, and 100%. Repeat PET/CT in HNSCC patients with an incomplete post-treatment scan can be valuable in obtaining diagnostic clarity. This can reduce the incidence of unnecessary biopsies and neck dissections.