Every enterprise management shall investigate return on investment whenever they need to implement protection measures for their machine and manufacturing system in order to reduce/ eliminate occurrence of industrial accidents. In general, enterprise management treat expenses related protection measures as additional cost, but these expenses shall be treated as investment to prevent from industrial accidents and to reduce/ eliminate additional cost by industrial accidents. Thus, it is important to clarify methods to measure return on investment. H. W. Heinrich announced analysis of probability of Industrial Accident Occurrence related with Return on Investment in 1926. Then, Simmons announced analysis of Cost caused by Industrial Accident related with Return on Investment in 1956. These analyses have been changed greatly due to changing times and environments. That's why this paper proposes a method of calculation of return on investment concerning with industrial accidents and its protection measures that shall be utilized in global. In this paper, we propose “Cost Characteristic of Occupational Accident” first. “Cost Characteristic of Occupational Accident” is a total cost caused by a maximum occupational accident by a machine and manufacturing system that does not implement any protection measures to prevent. The total cost shall include expenditure to recover from an occupational accident. Secondary, we define “Initial Investment for Protection Measures” that prevents a machine and manufacturing system form occurring occupational accidents. Then, compared with “Cost Characteristic of Occupational Accident” and “Initial Investment for Protection Measures”, relation between them shall be a guideline of return on investment for a specific machine and manufacturing system.