Coagulase-negative Staphylococci (CNS) are known to cause distinct types of infections in humans like endocarditis and urinary tract infections (UTI). Surprisingly, there is a lack of genome analysis data in literature against CNS particularly of human origin. In light of this, we performed genome mining and comparative genomic analysis of CNS strains Staphylococcus cohnii subsp. cohnii strain GM22B2, Staphylococcus equorum subsp. strain equorum G8HB1, Staphylococcus pasteuri strain BAB3 isolated from gall bladder and Staphylococcus haemolyticus strain 1HT3, Staphylococcus warneri strain 1DB1 isolated from colon. We identified 29% of shared virulence determinants in the CNS strains which involved resistance to antibiotics and toxic compounds, bacteriocins and ribosomally synthesized peptides, adhesion, invasion, intracellular resistance, prophage regions, pathogenicity islands. 10 unique virulence factors involved in adhesion, negative transcriptional regulation, resistance to copper and cadmium, phage maturation were also present in our strains. Apart from comparing the genome homology, size and G + C content, we also showed the presence 10 different CRISPR-cas genes in the CNS strains. Further, KAAS based annotation revealed the presence of CNS genes in different pathways involved in human diseases. In conclusion, this study is a first attempt to unveil the pathogenomics of CNS isolated from two distinct body organs and highlights the importance of CNS as emerging pathogens of health care sector.