In order to determine the allowable differential settlement between the bridge and the approach embankment, the vehicle comfort and safety of both the vehicle and the bridge were studied when the vehicle traveled through the transient section. A method based on comfort and safety was then proposed to determine the allowable differential settlement. The average weighted root-mean-square acceleration was used as the vehicle comfort evaluation index, the minimum dynamic wheel load was used as the vehicle safety evaluation index, and the local impact factor was used as the bridge safety evaluation index. The effect of vehicle running speed and differential settlement on the vehicle comfort level and local impact factor was analyzed. The results show that for expressways and first-class highways, the vehicle comfort is a more demanding requirement compared with vehicle safety. For secondary highways, the vehicle comfort is the most demanding requirement among the control indices for differential settlements, followed by bridge safety and vehicle safety. For highways below second-class, the bridge safety is the most demanding requirement, followed by vehicle comfort and vehicle safety. More rational control criteria for differential settlements based on vehicle comfort, vehicle safety and bridge safety can be proposed on the basis of the analysis method of this study.