OBJECTIVES: A 24-month randomised, open-label parallel group study in Type-2 diabetes patients compared the safety and efficacy of biphasic insulin aspart (BIAsp30/70) and biphasic human insulin (BHI30/70) injected twice daily before meals. Major hypoglycaemic episodes were reduced with BIAsp30/70 (annual rate 4.1%) versus BHI30/70 (annual rate 15.5%) and were significantly lower in the second study year (p=0.04). Glycaemic control did not differ between groups. A peer-reviewed, validated model projected the impact of the different rates of major hypoglycaemia events on long-term health economic outcomes in multinational settings. METHODS: The CORE Diabetes model employs standard Markov/Monte Carlo simulation techniques to describe long-term incidence and progression of diabetes-related complications. Transition probabilities were derived from major diabetes studies. The clinical effects of the comparators were derived from the trial described. The analysis was performed in multinational settings using published country-specific costs, health care resource utilization, clinical data, and recommended discount rates. A lifetime horizon and payer perspective was taken. Only direct costs were considered. Sensitivity analyses was performed. RESULTS: Discounted quality-adjusted life years (QALY) were improved by 0.15-0.22 years with BIAsp30/70 versus BHI30/70 depending on country specific discount rates. Increases in lifetime costs were seen with BIAsp30/70 in all settings. Costs per QALY were DKK61,922, 9784€, 12,840€, NOK38,911€, 14,068€, SEK76,495€, and £6,585 in the Danish, Finnish, German, Norwegian, Spanish, Swedish, and UK setting respectively. Results were most sensitive to assumptions regarding major hypoglycaemia rates, mortality following major hypoglycemic events, HbA1c changes and to the relative costs of BIAsp30/70 versus BHI30/70. CONCLUSIONS: Treatment with BIAsp30/70 was projected to result in additional QALYS and reduced health care costs associated with major hypoglycaemic events versus treatment with BHI30/70. The higher acquisition costs of BIAsp30/70 led to increased overall costs, but the incremental cost/QALY fell within the range generally considered to be cost-effective in each country.