Actinobacillus pleuropneumoniae, the cause of porcine pleuropneumonia, is responsible for major economic losses to the swine industry. One of the key considerations for rational vaccine design is the selection of stably expressed antigens. Phase variation is the random switching of gene expression, either ON-OFF switching of expression, or the expression of multiple allelic protein variants. Although phase-variable genes typically encode bacterial surface factors, a number of bacteria encode cytoplasmic DNA methyltransferases that are phase-variable. Random methyltransferase expression results in genome wide methylation differences within a bacterial population, resulting in gene expression changes via epigenetic mechanisms; these systems are known as a phasevarions (phase-variable regulon). In all described cases, phasevarions control expression of current and putative vaccine candidates. In this study we investigated the distribution of both Type I and Type III R-M systems from previously sequenced 210 whole genomes. As well, four prototype strains were investigated by fragment length analysis to determine the length of the repeat tracts. Target specificity of each unique methyltransferase in these strains was determined by Pacific Biosciences Single-Molecule, Real-Time (SMRT) sequencing. Our genome-based study revealed the presence of multiple, phase-variable Type I and Type III methyltransferases, with individual strains encoding up to three independently switching methyltransferases. This analysis also revealed a distinct conservation between particular methyltransferase alleles and serovar. Our analysis of the prototype strains demonstrated that all encoded methyltransferases identified are phase-variable. SMRT sequencing analysis demonstrated the presence of the first phase-variable cytosine-specific Type III methyltransferase discovered in bacteria. Analysis of changes in gene expression and phenotype influenced by phase variation of each Type III allele in the prototype strains showed that each distinct variant regulates different phasevarions, and has a unique influence on bacterial phenotype, such as antibiotic resistance, biofilm formation, and growth rate. Characterisation of these phasevarions will help define the stably expressed antigenic repertoire of A. pleuropneumoniae, and direct and inform development of a rationally designed vaccine against this major pathogen.