OBJECTIVES: Although it has been shown that rapid acting modern insulins such as insulin aspart (IAsp, NovoRapid) provide a more convenient and predictable onset of action compared to human soluble insulin (HSI), widespread acceptance of modern insulins will also depend on economic considerations. The aim of this study was to assess the cost-effectiveness of switching type 2 diabetes patients receiving HSI to IAsp, with or without oral hypoglycemic agents, in the Spanish and Italian settings. METHODS: Short-term data from the PREDICTIVE (Predictable Results and Experience in Diabetes through Intensification and Control to Target: an International Variability Evaluation) study were used to make long-term (35-years) projections of clinical and cost outcomes using the CORE Diabetes Model, a published and validated computer simulation model. Costs expressed in 2006 Euro (€) values and clinical outcomes were discounted at 3.5% per annum. The analysis was conducted from a third party health care payer perspective. RESULTS: In the Spanish and Italian settings, treatment with IAsp was projected to increase patient life expectancy by 0.101 and 0.164 years and to improve quality-adjusted life expectancy by 0.08 and 0.12 quality-adjusted life years (QALYs), respectively, compared to HSI. Treatment with IAsp was associated with a decrease in direct costs in the Spanish setting (reduced by €1382) and an increase in costs in Italy (€1874) compared to HSI over patient lifetimes. IAsp was dominant to HSI in Spain and associated with an incremental cost-effectiveness ratio of €15,593 per QALY gained in the Italian setting. CONCLUSION: IAsp treatment was projected to result in reduced diabetes-related complications and improved life expectancy compared to HSI in both settings investigated. The analysis indicated that IAsp would be dominant compared to HSI in Spain and in Italy would represent good value for money based on commonly quoted willingness-to-pay thresholds.