OBJECTIVES: To determine the cost-effectiveness of TRT with TU (NEBIDO®) compared with placebo for patients with ADAM and DM2, from the Brazilian Private Healthcare System perspective. METHODS: The study was a cost-effectiveness analysis based on Markov modeling to estimate costs and consequences of treatments. Epidemiological and efficacy data derived from a critical appraisal of the scientific literature. Only direct medical costs were considered. If available, costs of clinical events (CE) were obtained from burden of disease studies. If not, Brazilian official guidelines were obtained to determine the resources used to treat the CE. Drug, hospital daily admission rates, procedures and laboratory tests unit costs were obtained from Brazilian official databases. Costs and benefits were discounted at 5% yearly. Outcomes were expressed as CE avoided. Probability sensitivity analysis (PSA) was conducted to assess model robustness. Life time horizon was analyzed. RESULTS: The systematic review showed that although the absence of studies directly evaluating the impact of TU on cardiovascular events, their favorable influence on cardiovascular disease intermediate markers suggests that TU may have clinically relevant effect in patients at risk, especially in patients with metabolic syndrome and/or DM2. The analysis showed higher clinical benefits and costs for TU. Considering 100 patients, 75.2 and 140.0 CE happen in TU and placebo arms, respectively. The average time-horizon cost per patient was R$34,120(€14,896) and R$23,489(€10,255) for TU and placebo, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of R$16,390/CE avoided (€7,155/CE avoided). PSA demonstrated that in 83.2% of the simulations TU was more effective with higher cost and in 16.8% of the simulations TU was dominant compared to placebo. CONCLUSIONS: Our study demonstrated that TU have clinically relevant effect in reducing CE being highly cost-effective for ADAM  treatment in patients with DM2 at willingness-to-pay beyond R$19,000/CE  avoided (€8,296/CE avoided) (Brazilian GDP per capita).  PSA confirmed this determinist result.