Background The aim of this economic analysis was to model different strategies using pre-treatment nodal stage or nodal response assessment with CT or positron emission tomography (PET)/CT to determine the need for neck dissection. Methods A cost-minimization analysis was developed on the basis of probability data from a prospective study of PET-guided management of the neck in patients achieving a complete response at the primary site. Costs were derived from our institution's activity-based clinical costing system. The effect of uncertainty was tested with sensitivity and scenario analyses including nationally representative cost data. Results Strategies incorporating PET had a 7% rate for neck dissection compared with 44% for CT-guided and 90% for planned neck dissection. The cost per patient was A$16,502 for planned neck dissection, A$8014 for CT-guided, and A$2573 for PET-guided. A policy with PET used only for incomplete response on CT was the least-cost strategy (A$2111). Policies incorporating PET remained the most efficient for all sensitivity/scenario analyses. Conclusion The incorporation of PET/CT into nodal response assessment significantly reduced the number of unnecessary neck dissections and generated considerable cost savings in our cohort. 頲012 Wiley Periodicals, Inc. Head Neck, 2013