Introduction: Recently, many industrial exoskeletons for supporting workers in heavy physical tasks have beendeveloped. However, the efficiency of exoskeletons with regard to physical strain reduction has not been fully proved,yet. Several laboratory and field studies have been conducted, but still more data, that cannot be obtained solely bybehavioral experiments, are needed to investigate effects on the human body.Methods: This paper presents an approach to extend laboratory and field research with biomechanical simulationsusing the AnyBody Modeling System. Based on a dataset recorded in a laboratory experiment with 12 participantsusing the exoskeleton Paexo Shoulder in an overhead task, the same situation was reproduced in a virtual environmentand analyzed with biomechanical simulation.Results: Simulation results indicate that the exoskeleton substantially reduces muscle activity and joint reaction forcesin relevant body areas. Deltoid muscle activity and glenohumeral joint forces in the shoulder were decreased between54 and 87%. Simultanously, no increases of muscle activity and forces in other body areas were observed.Discussion: This study demonstrates how a simulation framework could be used to evaluate changes in internal bodyloads as a result of wearing exoskeletons. Biomechanical simulation results widely agree with experimental measurements in the previous laboratory experiment and supplement such by providing an insight into effects on the humanmusculoskeletal system. They confirm that Paexo Shoulder is an effective device to reduce physical strain in overheadtasks. The framework can be extended with further parameters, allowing investigations for product design and evaluation.