Background. The purpose of this study was to present our prospectively evaluated positron emission tomography (PET)-directed policy for managing the neck in nodepositive head and neck squamous cell carcinoma (NSCC) after definitive radiotherapy (RT) with or without concurrent systemic therapy. Methods. One hundred twelve consecutive patients who achieved a complete response at the primary site underwent a 12-week posttherapy nodal response assessment with PET and diagnostic CT. Patients with an equivocal PET underwent a repeat PET 4 to 6 weeks later. Patients with residual CT nodal abnormalities deemed PET-negative were uniformly observed regardless of residual nodal size. Results. Median follow-up from commencement of RT was 28 months (range, 13-64 months). Residual CT nodal abnormalities were present in 50 patients (45%): 41 PET-negative and 9 PET-positive. All PET-negative residual CT nodal abnormalities were observed without subsequent isolated nodal failure. Conclusion. PET-directed management of the neck after definitive RT in node-positive HNSCC appropriately spares neck dissections in patients with PET-negative residual CT nodal abnormalities.