Durability of the vehicle components needs special attention in the design step due to this fact that the loads on a vehicle are dynamic by their nature. Also, fatigue resistance of the vehicle body is quite important as it is the main load-bearing component among others. The main purpose of the present research is to simulate the spot weld failures of the vehicle body structure due to fatigue damage induced on the body during standardized maneuvers. This was accomplished by using a combination of multi-body dynamics and finite element analyses. To enhance the precision of the analysis, a thickness-dependent nugget diameter was utilized to model the spot welds. To validate the finite element simulations, three-sheet spot-welded specimens were tested and their fatigue lives were compared to numerical results. The findings of this study revealed that the damage to the vehicle body is not always proportional to the vehicle velocity and that depends on the degree of road roughness. Also, the results of simulations showed that the damage to the front part of the body is almost twice the rear part in terms of the number of spot weld failures. The effect of nugget diameter on the fatigue life of the spot welds was also investigated and it was found that the nugget diameter can change the fatigue life of the spot welds up to almost 100%. © 2020 Elsevier B.V.