The codon usage bias and the base composition variations in the available 12 complete iridovirus genome sequences have been investigated. We re-evaluated the number of open reading frames (ORFs) in each published iridovirus genome and analyzed its correlation against the genome size. The result shows that there is a direct relationship between the number of ORFs and the genome size. The codon usage patterns of these iridoviruses are found to be phylogenetically conserved. A significant variation in the base content among the 12 iridovirus genomes has been observed, with G+C content ranges widely from 27 to 55%. Moreover, the preferential use of bases in codons is different among higher and lower G+C content genomes. A preferential codon usage among viral genomes is also noticed. Effective number of codon (Enc) plot reveals that the G+C compositional constraint is the main factor that determines the codon usage bias. Relative synonymous codon usage analysis of methyltransferase containing as well as lacking viruses suggests that the codon usage is not influenced by the methylation-mediated mutation. In addition, the comparison of the codon usage of iridovirus hosts and the iridovirus genomes reveals that the host tRNA pool may be responsible for the base compositional constraint. This study represents the most comprehensive analysis to date for iridovirus codon usage patterns.