A framework for justifying ergonomic projects to the overall cost savings is developed which estimates the extent of musculoskeletal disorders (MSDs) exposures to a specific industry. A cost structure is developed to estimate the investment needed for an ergonomics program and the costs related to MSDs problems including workers' compensation costs, work-related costs, and labor turnover costs. Data was adopted from sources including Bureau of Labor Statistics (BLS), the Healthcare Cost and Utilization Project (HCUP-3), and estimates suggested in OSHA's former Ergonomics Standard. Top fifteen manufacturing industries with the highest MSDs rates were selected to apply the framework. Results showed that the overall cost savings among the fifteen selected industries come from ergonomics activities addressing the problem of overexertion (58%), bodily reaction (15%), and repetitive motion (27%). The study makes it possible to identify the proportion of exposure types that contribute to the overall costs of MSDs problems, so that managers can prioritize ergonomic analysis and control activities appropriately. Furthermore, based on the literature review, this is the first study to investigate the feasibility of using Real Options method to quantify ergonomic investment as well as an attempt to identify different types of real options in ergonomics program. Results showed that the value of ergonomics program could increase up to 2.43 times of the original value when real options are included.