Most manufacturing and assembly processes like stamping, clamping, interference fits introduce a pre-stress condition in components or assemblies. Very often these stresses are high enough and alter the mean stress state resulting in significant effect on fatigue life performance and thus cannot be ignored. If the pre-stress is compressive, it will increase the allowable stress range and improve fatigue life performance; on the other hand if these stresses are tensile, they will decrease the allowable stress range resulting in a degradation of fatigue life. At times it becomes critical to effectively introduce the pre-stress condition in order to accurately represent the stress state in an FEA based durability simulation. Accounting for the pre-stress state in FEA based constant amplitude loading fatigue life simulation is relatively straight forward, but when it comes to random variable amplitude multi-channel loads simulation, the problem becomes more complicated. In this paper, a method to include the pre-stress effect on vehicle components or assemblies and perform FEA based fatigue analysis when subjected to random road loads is practiced. This paper outlines the procedure used to calculate the pre-stress followed by the modified material curves and eventually performs FE based fatigue analysis using vehicle road load data. A couple of case studies are also included that will demonstrate the correlation of this FE based method to the physical component test results.