Aim. To assess the effect of rifaximin and a multi-strain probiotic on the intestinal microbiome and the indicators of cardiovascular risk in patients with coronary heart disease (CHD).Materials and methods. A study conducted during the 2016–2019 period included 120 people over 50 years old divided into 3 groups. Group 1 comprised patients with coronary heart disease receiving standard treatment. Group 2 comprised patients with coronary heart disease receiving additionally a probiotic (Bifidobacterium bifidum no less than 1x109 CFU; Bifidobacterium longum no less than 1x109 CFU; Bifidobacterium infantis no less than 1x109 CFU; Lactobacillus rhamnosus no less than 1x109 CFU) within 28 days. Group 3 comprised CHD patients receiving rifaximin for 7 days followed by addition of the multi-strain probiotic under test for 21 days. Group 4 consisted of healthy individuals, comparable in age and sex with the examined CHD patients. In group 4, blood and stool tests were performed once to provide a comparison with group 1. TMAO concentration was determined using liquid chromatography–mass spectrometry. To study the composition of fecal microflora, 16S sequencing was used followed by a graphical representation of the results. The results were analysed using the IBM SPSS 22.0 statistical data processing software.Results. An additional administration of the probiotic (Bifidobacterium bifidum no less than 1x109 CFU; Bifidobacterium longum no less than 1x109 CFU; Bifidobacterium infantis no less than 1x109 CFU; Lactobacillus rhamnosus no less than 1x109 CFU) is found to have no effect on the lipid profile and the platelet aggregation rate. Rifaximin therapy reduced the amount of total cholesterol, low density lipoproteins (LDL), very low density (VLDL) lipoproteins and triglycerides (p <0.05), although not affecting the level of high density lipoproteins (HDL). TMAO showed a statistically insignificant (p>0.05) downward trend in all groups. The composition of the fecal microbiota, at the end of administration of the probiotic, showed an increase in the proportion of bacteria of the Streptococcaceae, Lactobacillaceae, Enterobacteriaceae families and a decrease in the Ruminococcaceae family (p>0.05). After rifaximin therapy, a decrease in the proportion of bacteria of the Clostridiaceae (p <0.05) and Peptostreptococcaceae (p <0.05) families, a decrease in Enterobacteriaceae (p > 0.05) family and a decrease in the Clostridium and Escherichia/Shigella (p > 0.05) genera was observed. The use of the probiotic after a course of treatment with rifaximin did not have a significant effect on the composition of the microflora. In general, the high variability of fecal microbiota between different patients (significantly superior to intergroup differences) does not allow us to draw unambiguous conclusions.Conclusions. The use of a multi-strain probiotic as an additional therapy in patients with coronary heart disease within 28 days did not have a significant effect on lipid metabolism, TMAO level and the composition of fecal microflora. The consecutive use of rifaximin and the probiotic had a beneficial effect on such factors as lipid metabolism (decrease in the level of total cholesterol, LDL, VLDL, triglycerides), but did not affect the concentration of TMAO and the composition of the intestinal microflora in patients with coronary heart disease.