Abstract Background The purpose of this study was to present our prospectively evaluated positron emission tomography (PET)‐directed policy for managing the neck in node‐positive head and neck squamous cell carcinoma (N+HNSCC) 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. © 2011 Wiley Periodicals, Inc. Head Neck, 2011