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This Special Issue aims to provide a platform for sharing novel methodologies and applications that can be effectively utilized for the development of ergonomic designs of human-system interactions. Areas of ergonomic approaches and applications include cognition, anthropometry, biomechanics, safety, macro-ergonomics, human-system integration, user-centered design, universal design, experience design, sustainable design, affective computing, autonomous systems, VR/AR/MR, aging, healthcare, neuro-ergonomics, musculoskeletal disorders, human-robot interaction, and exoskeletons. Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere.