The continuously increasing mechanical and thermal loads of modern engines require optimization of the designs with incorporation of a wide range of different aspects. Application of advanced computer simulations in the development process for most engine components is well established, leading to the creation of well optimized products. However, the optimization of such design variables ike the firing order, which influences engine operation in several disciplines, is still challenging. Considering the ever increasing peak firing pressure requirements, the layout of the firing order in multi-cylinder commercial engines is an efficient way to reduce crank train / overall engine vibration and main bearing loads, whilst controlling engine balancing and preserving adequate gas exchange dynamics. The proposed general firing order selection process for four-stroke engines and, in particular, its first part being the optimization of the firing order based on crank train torsional vibration, is the main topic of this paper. The exemplary study for a V20 high speed commercial Diesel engine regarding the influence of the firing sequence on crank train torsional vibration has been conducted with the multibody dynamics simulation software “FEV Virtual Engine”. It addresses various engine crankshaft layouts and engine applications.