Little research has been conducted into the cost and prevention of self-harm in the workplace. Aims: To quantify the economic cost of self-harm and suicide among New South Wales (NSW) construction industry (CI) workers and to examine the potential economic impact of implementing Mates in Construction (MIC). Method: Direct and indirect costs were estimated. Effectiveness was measured using the relative risk ratio (RRR). In Queensland (QLD), relative suicide risks were estimated for 5-year periods before and after the commencement of MIC. For NSW, the difference between the expected (i.e., using NSW pre-MIC 2008Ð2012 suicide risk) and counterfactual suicide cases (i.e., applying QLD RRR) provided an estimate of potential suicide cases averted in the post-MIC period (2013Ð2017). Results were adjusted using the average uptake (i.e., 9.4%) of MIC activities in QLD. Economic savings from averted cases were compared with the cost of implementing MIC. Results: The cost of self-harm and suicide in the NSW CI was AU $527 million in 2010. MIC could potentially avert 0.4 suicides, 1.01 full incapacity cases, and 4.92 short absences, generating annual savings of AU $3.66 million. For every AU $1 invested, the economic return is approximately AU $4.6. Conclusion: MIC represents a positive economic investment in workplace safety.