Background: 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 [2008β2012] suicide risk) and counterfactual suicide cases (i.e., applying QLD RRR) provided an estimate of potential suicide cases averted in the post-MIC period (2013β2017). 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 527millionin2010.MICcouldpotentiallyavert0.4suicides,1.01fullincapacitycases,and4.92shortabsences,generatingannualsavingsofAU3.66 million. For every AU 1invested,theeconomicreturnisapproximatelyAU4.6. Conclusion: MIC represents a positive economic investment in workplace safety