OBJECTIVES: Haemophilia A causes a considerable burden on society. While prophylaxis in children aged ≤2y is now a gold standard treatment, the benefits of late secondary prophylaxis are still controversial. Aim of this study is to estimate the cost-utility of antihemophilic factor rFVIII-FS (Kogenate® FS) in secondary prophylaxis vs on-demand regimen from the Italian healthcare system (NHS) and society perspective. METHODS: An individual patient simulation model was adapted to estimate the costs and outcomes associated with secondary prophylaxis and on-demand treatment. The model follows a hypothetical cohort of 1000 patients in a lifetime period. The POTTER observational study represented the source for clinical data such as clothing factors regimens and consumption, adherence to prophylaxis, risk of joint and total bleeds, quality-of-life (QOL) scores and productivity loss. For other data such as intracranial haemorrhage and major surgery rate, data from published literature were used. Drugs costs were estimated using prices reimbursed by the NHS while hospital costs were estimated with national hospital (inpatient and outpatient) tariffs. Caregivers’ or patients’ productivity loss was estimated with Italian daily Gross Net Product per-capita. Costs and benefits were discounted at 6.0% in line with published economic evaluations on this subject. Incremental cost-effectiveness ratios (ICERs) were calculated. Model outcomes are expressed in terms of costs per quality-adjusted-life-years (QALY). RESULTS: As expected, mean lifetime costs are higher with secondary prophylaxis than with on-demand treatment. Secondary prophylaxis however determines better outcomes in bleeding reduction and better QoL. Using the NHS perspective (considering only direct healthcare costs) secondary prophylaxis shows an ICER vs on-demand of €51,202/QALY; a more favourable ICER of €45,432/QALY is shown when considering also indirect costs. CONCLUSIONS: Despite the high cost of the pharmacological treatment, antihemophilic factor rFVIII-FS in secondary prophylaxis represents a cost-effective approach compared with on-demand treatment.