Objectives:This paper discusses the development of a cost-estimation model for work-related stress based on psychosocial risk exposure and absence from work. It presents findings from its implementation and evaluation in two organizations in Italy, using national-level tools developed by the Italian Workers’ Compensation Authority (INAIL). It also provides recommendations for the development of similar cost-calculation methods in other countries.Methods:The cost-estimation model was based on the human capital approach using an indirect cost indicator: loss of productivity due to days of absence attributable to work-related stress. Furthermore, the population attributable fraction (PAF) epidemiological measure was used to calculate the impact of exposure to work-related stress on the basis of data collected through validated tools developed by INAIL and salary cost data.Results:The developed model was implemented and evaluated in two organizations, the first in healthcare (N=1014) and the second in public administration (N=534). In the first case, it was found that absence related to work-related stress cost the organization €445 000. In the second case, the cost was €360 000.Conclusions:The proposed model provides an example of how organizations can incorporate well-established indicators associated with work-related stress (eg, various types of absence, psychosocial risk perception, loss of productivity on the basis of salary costs) in a practical way in cost estimations of work-related stress. Such cost estimation can be applied in other countries and organizations to establish the economic and business case of managing work-related stress.