The gut microbiome has been linked to cardiovascular diseases, but its composition and functional capacity in relation to these diseases have not been systematically examined. This study performs a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of *Enterobacteriaceae* and *Streptococcus* spp., and in potential for metabolism or transport of molecules important for cardiovascular health. The ACVD status, not current drug use, is the major distinguishing feature in this cohort. Common alterations in the gut microbiome are observed in ACVD, type 2 diabetes (T2D), obesity, liver cirrhosis, and rheumatoid arthritis (RA), suggesting a less fermentative and more inflammatory gut environment in these diseases. The study provides a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD and other related diseases.The gut microbiome has been linked to cardiovascular diseases, but its composition and functional capacity in relation to these diseases have not been systematically examined. This study performs a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of *Enterobacteriaceae* and *Streptococcus* spp., and in potential for metabolism or transport of molecules important for cardiovascular health. The ACVD status, not current drug use, is the major distinguishing feature in this cohort. Common alterations in the gut microbiome are observed in ACVD, type 2 diabetes (T2D), obesity, liver cirrhosis, and rheumatoid arthritis (RA), suggesting a less fermentative and more inflammatory gut environment in these diseases. The study provides a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD and other related diseases.