Some of the significant issues associated with the Prevention through Design (PtD) research initiative of the National Institute for Occupational Safety and Health (NIOSH), are discussed. The research initiative of the institute focuses on some significant factors, such as the economic case for PtD, design-related casualty of occupational injuries and illness, the development of PtD devices, tools, and processes, worker, machine, structure, and environment interaction, diffusion sustainability and the communication of design innovations, and methodologies for PtD research. The institute has started the initiative, as research needs to conducted, to examine the costs associated with the process of PtD, manufacturing, and construction of specific safe design. The research initiative will also investigate the economic impact of the absence of safety issues into the design process.