Investigating the genetic variability among natural WSSV populations is a novel approach to understand the evolution and pathogenesis of this virus. We characterized the number of repeat units located in the variable number of tandem repeat regions (VNTR) of ORF75, ORF94 and ORF125 (WSSV-TH strain; Van Hulten et al., 2001) from 662 WSSV-DNA samples collected from 104 shrimp ponds. The results showed that: (i) a high genetic diversity of WSSV isolates in the small scale shrimp farming operations in the Mekong delta, Viet Nam, occurred; (ii) the pattern of repeat regions in ORF94, ORF125 was positively correlated with disease status (disease outbreak or not); (iii) low repeat unit numbers have a significantly higher prevalence in outbreak ponds compared to non-outbreak ponds, especially for ORF94, suggesting that this VNTRs region is useful for monitoring WSSV populations for virus outbreak status. There is no significant correlation of VNTR repeat unit structure and shrimp cultivation practices. These findings add to our understanding of the role of WSSV population structure and disease outbreaks.