Due to increasing automation, the number and complexity of technical components have increased in the medical context (e.g., in the clinic or in the home care sector) in recent years. Besides new effective and efficient therapeutic and diagnostic options, these devices entail a wide range of functions and very complex (often computer-based) user interfaces that may lead to human-induced risk potential. A systematic and early human risk analysis and a usability evaluation allow medical device manufacturers to identify and control risks within the human-machine interaction very efficiently. At the Department of Medical Engineering in the Helmholtz Institute for Biomedical Engineering at the RWTH Aachen University, a formal-analytical methodology and a corresponding software tool for prospective human-risk analysis and model-based usability evaluation has been developed. Based on a twofold approach, user interactive process sequences and their potential impacts on the overall process are identified and the resulting use-related risks are assessed. For this, the tasks are categorized (in system and user tasks) and modeled and temporally related within the framework of a high-level task analysis. Within a subsequent cognitive low-level task analysis, potentially critical parallel process sequences are then tested in order to detect a potential resource overload of the user. The subsequent corresponding human-risk analysis is developed according to a knowledge base (checklist) of taxonomies related to human error. The HiFEM (human-function effect modeling) methodology is universally applicable and can be used for the evaluation of human-computer interfaces as well as for the analysis of purely mechanical control interfaces and simple hand-held instruments (such as a scalpel and implant). In a comparative study, the HiFEM method clearly outperforms the classic FMEA (failure modes and effects analysis) process with regard to effectiveness, efficiency, learnability, and user satisfaction. Especially small and medium-sized enterprises that constitute the medical device industry can be supported by the new methodology in the context of risk management according to ISO 14971 as well as usability engineering in accordance with IEC 62366 and IEC 60601-1-6 as well as EN ISO 9241.