Whole genome sequencing is becoming a leading technology in typing and epidemiology of microbial pathogens, but the increase in genomics information necessitates significant investment in bioinformatic resources and expertise, and currently used methodologies struggle with genetically heterogeneous bacteria such as the human gastric pathogen Helicobacter pylori. Here we demonstrate that the alignment-free analysis method Feature Frequency Profiling (FFP) can be used to rapidly construct phylogenetic trees of draft bacterial genome sequences on a standard desktop computer, and that the coupling with in silico genotyping methods gives useful information for comparative and clinical genomics and molecular epidemiology applications. FFP-phylogenetic trees of seven gastric Helicobacter species matched those obtained by analysis of 16S rDNA and ribosomal proteins, and FFP- and core genome single nucleotide polymorphism-based analysis of 63 H. pylori genomes showed again comparable phylogenetic clustering, consistent with genomotypes assigned using multi-locus sequence typing (MLST). Analysis of 377 H. pylori genomes highlighted conservation of genomotypes and linkage with phylogeographic characteristics, and predicted the presence of an incomplete or non-functional cag pathogenicity island in 18/276 genomes. In silico analysis of antibiotic susceptibility markers suggests that most H. pylori hspAmerind and hspEAsia isolates are predicted to carry the T2812C mutation conferring low level clarithromycin-resistance, while levels of metronidazole resistance were similar in all MLST-types. In conclusion, the use of FFP phylogenetic clustering and in silico genotyping allows determination of genome evolution and phylogeographic clustering, and can contribute to clinical microbiology by genomotyping for outbreak management, and the prediction of pathogenic potential and antibiotic susceptibility.