The complete genome of the Villegas-Glisson/University of Georgia (VG/GA) strain of Newcastle disease virus (NDV) and that of a plaque purified clone (clone 5) exhibiting a respiratory phenotype were sequenced and analyzed. The VG/GA strain, isolated from the intestine of healthy turkeys, replicates in the respiratory and intestinal tract of chickens. It is used worldwide as a vaccine strain and its tissue tropism is extremely important for protection against velogenic viscerotropic NDV which targets both intestinal and respiratory epithelia, inducing severe gross and microscopic damage. The clone 5, a plaque purified clone from the VG/GA strain, cannot be recovered from the intestine of infected birds, suggesting a respirotropic nature. A modified primer sequence-independent amplification method was used to sequence the complete coding regions of both viruses and to assess phylogenetic relationships and genomic basis for phenotype differences. The phylogenetic analysis grouped the VG/GA strain and the clone 5 within class II, genotype II viruses and showed that they are greater than 99.9% identical with only 5 nucleotides differences. Both are closely related to classic vaccine strains, such as LaSota and B1. Only 3 amino acid differences at the fusion protein differentiated the VG/GA strain from the clone 5. These differences may explain the differential phenotype observed in the VG/GA strain and are discussed.