Varicella-Zoster virus (VZV) causes varicella as a primary infection following which it becomes latent in human ganglia and then reactivates to cause herpes zoster. VZV vaccines are used to prevent primary infection with varicella, and also to reduce the incidence of viral reactivation causing herpes zoster and post-herpetic neuralgia. To gain further insights into the molecular basis of their attenuated virulence, we used long oligonucleotide microarrays to determine the lytic transcriptomal profiles of two vaccine VZV strains (Merck and GSK) compared with the Oka parental (P-Oka) strain. There was a global downregulation of transcription of both vaccines relative to P-Oka, although this downregulation was more extensive in the GSK strain. Open Reading Frames (ORFs) 62 and 14 were the most transcriptionally downregulated on the arrays for both vaccines compared with the parental strain.