OBJECTIVE: To assess, in a real life setting, the predictive validity of a health-economic model that had been applied for the Belgian reimbursement submission of voriconazole in proven and probable invasive aspergillosis. METHODS: An observational study was designed to prospectively collect health-economic data of patients with invasive aspergillosis starting treatment with voriconazole. The same direct costs as in the model were considered: costs for hospital stay, diagnostic procedures, treatment/monitoring of side effects, outpatient care and use of anti-fungal drug(s). Resource utilization, expressed in physical units, was multiplied with unit costs from the public payer's perspective. Costs were expressed as total costs and costs for switchers/non-switchers from initial voriconazole treatment. Effectiveness was expressed as clinical response and survival rate at day 84. RESULTS: A total of 115 patients were included. The average total cost was €14,153 (C.I.: €11,493; €16,812). This was below the cost predicted by the model (€21,298). The difference was mainly caused by shorter hospitalization in this study (9.59 days) than assumed in the model (29.4 days). On average the total cost for switchers/non-switchers amounted to €16,216/€10,067 in this study, which was below the estimated cost of €27,586/€18,783 in the model, mainly due to a lower hospitalization cost. The clinical response rate (50% successful outcome) as well as the infection related survival rate (86.7%) were in line with the ones applied in the model and reported from the clinical trials (52% and 87.5% respectively). The overall survival rate was lower compared to the model (58% vs. 70.8%), likely due to treating patients with poor prognosis at baseline who would have been excluded from the clinical trial. CONCLUSIONS: This observational study demonstrated that the health-economic model provided an overestimate of the real life costs with voriconazole and a good estimate of clinical response and survival rates.