Analysis of Asian H5N1 avian influenza (AI) virus hemagglutinin (HA) genes shows a common origin, but the virus has evolved into at least three major clades (clades 0, 1, and 2) over the last 13 years. Previous reports of Vietnam viruses have documented predominantly clade 1 viruses. Unexpectedly, 19 viruses from northern Vietnam isolated in December 2005 fell into clade 2. These viruses further clustered into two distinct sublineages. Representative viruses from each sublineage were chosen for antigenic and pathogenic evaluation. Two distinct antigenic groups correlating with the genetic information were present when comparing hemagglutination inhibition (HI) titers. All viruses were highly virulent not only in chickens, killing them within 2 days of experimental inoculation, but also in 2- and 5-week-old Pekin ducks, causing 100% mortality within 4 days of challenge. The information gained about these viruses provides insight with regards to implementing control programs, including vaccine seed strain selection.