Introduction: Recently, many industrial exoskeletons for supporting workers in heavy physical tasks have been developed. 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 by behavioural experiments, is needed to investigate effects on the human body. Methods: This paper presents an approach to extend laboratory and field research with biomechanical simulations using the AnyBody Modelling System. Based on a data set recorded in a laboratory experiment with 12 participants using the exoskeleton Paexo Shoulder in an overhead task, the same situation was reproduced in a virtual environment and analysed with biomechanical simulation. Results: Simulation results indicate that the exoskeleton substantially reduces muscle activity and joint reaction forces in relevant body areas. Deltoid muscle activity and glenohumeral joint forces in the shoulder were decreased between 54 % 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 body loads 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 human musculoskeletal system. They confirm that Paexo Shoulder is an effective device to reduce physical strain in overhead tasks. The framework can be extended with further parameters, allowing investigations for product design and evaluation.