Design optimization of multi-body systems is challenged by the highly non-linear and computationally expensive (for large-scale systems) nature of many multi-body responses. In this paper, a sequential approximate optimization method is presented in order to achieve accurate and ef cient design optimization of multi-body systems under impact loads. The sequential approximate optimization method is obtained by coupling a conventional optimization algorithm with a statistical model building technique, response surface methodology (RSM). In this method, a multi-body optimization problem is approximated as a series of simpler subproblems, using RSM and a genetic algorithm, before it is solved by a numerical optimization algorithm. The approximate optimization method is applied to several multi-body impact problems. These include a linear impact absorber and lumped-mass systems representing simpli ed vehicle-barrier and vehicle-vehicle frontal impacts. The effect of the choice of various approximation methods is also addressed. The results demonstrate that the use of RSM coupled with conventional optimization methods leads to ef cient and effective design tools for multi-body systems under impacts.