The rotational self-loosening of bolted joints under cyclic loading is a process, which means a screw rotation against the assembly direction by periodic load cycles. Thus, the preload balance is released and the clamping function is no longer maintained. The effect is well known, but prevention is usually performed experimentally only after occurrence of self-loosening events. The paper gives a systematic presentation of the dimensioning and the possibility to consider self-loosening in the development process. The procedure for self-loosening dimensioning and the influences are demonstrated with safety-relevant multi-bolted connections from the automotive industry. The aim of this paper is to provide a numerical design method with finite element analysis for detecting and understanding of the self-loosening process at bolted joints. Another focus of the work is to investigate the self-loosening behaviour under combined loading with a superposition of translation and rotation. Combined loading can lead to self-loosening even before reaching the limit of self-loosening for transverse loading. The computational results of the numerical simulation (FEA) are compared with experimental investigations.