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Background: Psychosocial interventions following self-harm in adults, in particular cognitive behavioral therapy (CBT), can be effective in lowering the risk of repeated self-harm. Aims: To evaluate the cost-effectiveness of CBT for reducing repeated self-harm in the Australian context. Method: The current study adopted the accessing cost-effectiveness (ACE) approach using return-on-investment (ROI) analysis. Uncertainty and sensitivity analyses (Sas) tested the robustness of the model outputs to changes in three assumptions: general practitioner referral pathway (SA1), private setting intervention delivery (SA2), and training costs (SA3). Results: The intervention produced cost savings of A$ 46M (95% UI -223.7 to 73.3) and A$ 18.3M (95% UI -86.2 to 24.6), subject to the effect of intervention lasting 2- or 1-year follow-up. The ROI ratio reduced to 5.22 in SA1 (95% UI -10.1 to 27.9), 2.5 in SA2 (95% UI -4.8 to 13.3), and 5.1 in SA3 (95% UI -9.8 to 27.8). Limitations: We assumed that the effectiveness would reduce 50% within 5 years in the base case, and we used Australian data and a partial social perspective. Conclusions: The current study demonstrated cost-effectiveness of CBT for adults who have self-harmed with the return-on-investment ratio of A$ 2.3 to $6.0 for every A$ 1 invested.