OBJECTIVES: Thrombocytopenia limits the use of interferon (INF) based regimens in chronic hepatitis C virus (HCV) patients. Eltrombopag, a thrombopoietin-receptor agonist, effectively elevates platelet count allowing optimal INF-treatment. The objective of the present study was to assess the cost-effectiveness as support treatment in chronic HCV infected patients with thrombocytopenia to enable INF-based treatment regimens from the Spanish Health System perspective. METHODS A two-phase individual-level model was developed to evaluate the cost-effectiveness of eltrombopag treatment in thrombocytopenic HCV-patients over a lifetime horizon. Individual-level models are more flexible and provide more accurate estimations than Markov approaches. One million patients were simulated using data from trials ENABLE 1 and 2 and local studies. In the first phase, a discrete event simulation was used to recreate patient events during INF-treatment. When eltrombopag was considered, patients underwent an initial pre-INF treatment with eltrombopag. Those that failed to reach INF-label platelet count did not receive INF-based regimens. In the second phase, a microsimulation was used to emulate each patient from treatment discontinuation to death. Health states included fibrosis (F0, F1/2, F3, F4), liver decompensation, hepatocelullar carcinoma, liver transplant and death. Transition probabilities for each 1-month cycle, utilities and direct health-care costs (€ 2014) were obtained from literature and national databases. A 3% annual discount was applied to costs and health outcomes. Sensitivity analysis with 0% and 5% discount rates were performed. RESULTS Eltrombopag was associated with an average increment of 0.58 quality-adjusted life years (QALY) and an additional cost of €17,084.47/patient. The average incremental cost effectiveness ratio (ICER) was 29,808.26 €/QALY. Considering a €30,000 threshold, eltrombopag was cost-effective in 59.12% of cases. This proportion remained similar with 5% (56.7%) and 0% (63.25%) discount rates. CONCLUSIONS With the premises considered in this study, eltrombopag in HCV patients could be considered cost-effective from the Spanish Health System perspective.