Validation of a computational fluid dynamics (CFD) model used to simulate turbulent exchange in an anatomically detailed human upper airway with realistic breathing states is provided. Proper model validation is vital in confirming that temporal mixing and species distribution are accurate, therefore making the model useful in generalized turbulent mixing studies of the upper airway. Numerous levels of refinement were tested for time-step and mesh independence. Higher and lower rigor groups of modeling methodologies involved spatial discretization schemes, gradient reconstruction methods, transient formulations, and turbulence frameworks. A dual mesh independence study revealed that the rate of approach to mesh independence is a function of computational rigor and that multiple mesh independence studies should be carried out in parallel. The final validated model consisted of the finest mesh used in this study (8 × 106 cells), a time-step equating to 4000 timesteps per breath cycle, and higher rigor modeling methodologies. While its results were within the acceptable deviation from the experimental data, it was not as close as the model that utilized the coarsest mesh (∼2 × 106 cells), the fewest timesteps per breath cycle (128 timesteps per breath cycle), and lower rigor methodologies. Though the latter model was closer to the experimental data, it was proven to not be numerically independent, highlighting the importance of utilizing a myriad of metrics to prove numerical independence. Restricting independence studies to only using metrics from experimental comparisons is insufficient for proper validation.