Three methodological approaches were applied to analyze whether the cost-effectiveness of drotrecogin alfa (activated) (Xigris) as an adjunct to standard care compared with standard care alone is a cost-effective alternative for the treatment of Swedish patients with severe sepsis and organ dysfunction. Health-economic model simulations were applied to (1) Swedish treatment pattern data, (2) international trial data and local unit prices, and (3) Swedish local patient data combined with trial age structure to adjust for differences in the age structure between the trial and the Swedish patient sample. The methodological approach had no effect on the overall conclusion that the intervention was cost-effective in the treatment of Swedish patients with severe sepsis and organ dysfunction. However, the cost-effectiveness ratios were sensitive to the approach applied. The results indicate the importance of collecting not only information on local prices but also information about treatment pattern and patient characteristics when conducting country-specific health-economic model applications.