Introduction: Media guidelines for the responsible reporting of suicide are a recognized universal suicide prevention intervention. While implemented in nu-merous countries, including Australia, little is known about whether they are cost- effective. We aimed to determine the cost- effectiveness of Mindframe, the national initiative implementing media guidelines in Australia. Method: We conducted a modelled economic evaluation (5- year time- horizon) incorporating two types of economic analysis: (i) return- on- investment (ROI) comparing estimated cost savings from the intervention to the total interven-tion cost, and (ii) cost- effectiveness analysis comparing the net intervention costs to health outcomes: suicide deaths prevented and quality- adjusted life- years (QALYs). We also included uncertainty analyses to propagate parameter un-certainty and sensitivity analyses to test the robustness of the model outputs to changes in input parameters and assumptions. Results: The estimated ROI ratio for the main analysis was 94:1 (95% uncer-tainty interval [UI]: 37 to 170). The intervention was associated with cost savings of A$596M (95% UI: A$228M to A$1,081M), 139 (95% UI: 55 to 252) suicides prevented and 107 (95% UI: 42 to 192) QALYs gained. The intervention was dominant, or cost-saving, compared with no intervention with results being robust to sensitivity analysis but varying based on the conservativeness of the parameters entered. Conclusion: Mindframe was found to be cost-saving, and therefore, worthy of investment and inclusion as part of national suicide prevention strategies.