In the winter 2005/2006 H5N1 highly pathogenic avian influenza virus (HPAIV) reached Western Europe and caused numerous deaths primarily in migratory water birds. Between February and April 2006 34 cases of H5N1 HPAIV-infected dead water fowl were identified in Switzerland, almost exclusively occurring in the Lake Constance area, a large overwintering area for migratory birds in the eastern part of the country. In total, 13 of these virus isolates were genetically characterized in the present study by full-length nucleotide sequence analysis of the hemagglutinin and neuraminidase-coding region. All viruses could be confirmed as HPAIV based on the amino acid sequence of their hemagglutinin cleavage site. Phylogenetic analysis revealed that all the virus isolates were highly similar to each other and to other H5N1 strains found in neighboring countries. All analyzed Swiss virus isolates belonged to the influenza virus subclade 2.2.1.