To our knowledge, no prior multicenter clinical trial has reported interobserver agreement of F-FDG PET/CT scans for staging of clinical N0 neck in head and neck cancer. A total of 287 participants were recruited. For visual analysis, positive nodal uptake of F-FDG was defined as uptake visually greater than activity seen in the blood pool. The negative predictive value of the F-FDG PET/CT for N0 clinical neck was 86% or above for visual assessment (95% CI, 86%-88%) for the 2 central readers and above 90% (95% CI, 90%-95%) for SUV for central reads and site reads dichotomized at the optimal cutoff value of 1.8 and the prespecified cutoff value of 3.5, respectively. The κ coefficients between the 2 expert readers and between central reads and site reads varied between 0.53 and 0.78. The NPV of the F-FDG PET/CT for N0 clinical neck was 86% or above for visual assessment and above 90% for SUV cut points of 1.8 and 3.5 with moderate to substantial agreements.