Tire nonuniformity may affect vehicle ride comfort quality especially while vehicles are running at highway speeds. Spindle force variations in the radial, tangential, and lateral directions are normally used as parameters evaluating tire high speed uniformity performance. An interesting physical phenomenon—directionality of tangential force variation has been observed for many tires. The directionality of tangential force variation means that tangential force variation is different when a tire is measured in the clockwise and counter-clockwise directions under the same test conditions. In this paper, a theory is developed to explain the interesting physical phenomenon. Simulation and analysis are conducted using a dynamic tire model. It is found that the directionality of tangential force variation is caused by the interaction of different types of nonuniformities in tires such as mass and geometry variations.