During the last decade there has been an apparent increase in the prevalence of counterfeit medicines in developing as well as developed countries. The pivotal antimalarial artesunate has been counterfeited on a large scale in SE Asia. In this work, the possibilities of Raman spectroscopy are explored as a fast and reliable screening method for the detection of counterfeit artesunate tablets. In this study, 50 'artesunate tablets', purchased in SE Asia, were examined. This spectroscopic method was able to distinguish between genuine and counterfeit artesunate and to identify the composition of the counterfeit tablets. These contained no detectable levels of artesunate, but consisted mostly of starch, calcite (CaCO3), and paracetamol (4-acetamidophenol). In one particular case an admixture of rutile (TiO2) and artesunate was detected. The results of the investigation by Raman spectroscopy were in agreement with those of colorimetric tests and of liquid chromatography-mass spectrometry on the artesunate. Moreover, principal components analysis (PCA) was combined with hierarchical cluster analysis to establish an automated approach for the discrimination between different groups of counterfeits and genuine artesunate tablets. These results demonstrate that Raman spectroscopy combined with multivariate analysis is a promising and reliable methodology for the fast characterization of genuine and counterfeit artesunate antimalarial tablets. Copyright (C) 2006 John Wiley & Sons, Ltd.