Background: Although the Streptococcus genus includes mainly pathogenic species, Streptococcus thermophilus is a widely used dairy starter culture of great economic importance for the food industry. S. thermophilus has been adapted to milk probably through a degenerative evolution process that has led to the loss of typical streptococcal pathogenic traits. Objectives: The genome sequence of the yogurt isolate S. thermophilus ACA-DC 29 was analyzed for assessing the technological potential of this strain. Comparative genomics analysis was also performed between the genome of ACA-DC 29 and the existing complete genome sequences of S. thermophilus. Methods:The genome sequence of ACA-DC 29 was annotated using online annotation tools. Full chromosome alignments were calculated with Progressive Mauve. The pangenome, the core genome and the unique genes were predicted with the GView Server. The genomic islands, the CRISPRs and the antimicrobial peptides were predicted with IslandViewer, CRISPRcompar and BAGEL3, respectively. Conclusions:The analysis of the S. thermophilus ACA-DC 29 genome sequence revealed the absence of pathogenic features. Genes related to the adaptation to milk were identified. Full chromosome alignments showed a high degree of synteny among the different strains. The pangenome of the ten strains comprised of approximately 2,300 genes. Concerning the ACA-DC 29 strain, approximately 250 unique genes involved in various biological processes were also identified. Further analysis indicated that several of them may have been acquired through horizontal gene transfer. Five potential antimicrobial peptides and two CRISPR systems, which may confer resistance against phages, were also predicted.