Background: The average sequence divergence between each enterovirus 71 (EV-71) subgenotype has been previously established using VP1 gene sequences. However, VP1 only encompasses 12% of the complete genome and other non-structural genomic regions are also phylogenetically informative. In the present study, using the complete EV-71 genome sequences, pairwise sequence comparisons (PASC) were analyzed to standardize the genotyping of EV-71. Methods: With the recent availability of 41 complete EV71 genomes of various subgenotypes and 12 complete human enterovirus A(HEV-A) genomes, genome sequence similarities were visualized by plotting the frequency distribution of the pairwise identity percentages. Results: Using the complete genome, the average sequence divergences between HEV-A and EV-71 were 26.15% (22—28%) at the nucleotide level and 15.01% (9—21%) at the amino acid level. The average nucleotide sequence divergence between EV-71 genotypes (A, B and C) was 19.64% (17—21%), while between and within the subgenotypes (B2-B5 and C1-C4) were 10.75% (6—14%) and 3.09% (1—5%) respectively. Based on these results, subgenotype C4 which has nucleotide sequence divergence of 18.13% (17—20%) when compared with other subgenotypes C (C1C3) exceeded the cutoff divergence value assigned for EV-71 subgenotyping, and should be redesignated as a new genotype D. On the other hand, subgenotype B5 which has only average nucleotide sequence divergence of 5.56% (4—7%) when compared with other subgenotypes B4 did not justify its designation as a new subgenotype. Conclusion: The average divergence values generated through PASC between members of the EV-71 and HEV-A can systematically delineate the HEV-A serotypes, EV-71 genotypes and subgenotypes.