Automotive and aircraft assembly process rely on fixtures to support and coordinate parts and subassemblies. Fixture layout in multi-station panel assemblies has a direct dimensional effect on final products and thus presents a quality problem. This paper describes a methodology for fixture layout design in multi -station assembly processes. An optimal fixture layout improves the robustness of a fixture system against environmental noises, reduces product variability, and eventually leads to manufacturing cost reduction. One of the difficulties raised by multi-station fixture layout design is the overwhelmingly large number of design alternatives. This makes it difficult to find a global optimality and, if an inefficient algorithm is used, may require prohibitive computing time. In this paper, simulated annealing is adopted and appropriate parameters are selected to find good fixture layouts. A four-station assembly process for a sport utility vehicle (SUV) side frame is used throughout the paper to illustrate the efficiency and effectiveness of this methodology.