Context center dot One common and serious cardiovascular complication of chronic renal failure (CRF) is coronary heart disease (CHD). CRF can lead to an imbalance of patients' gut microbiota, and changes in intestinal flora might heavily affect CRF's development. Objective center dot The study intended to investigate the changes in intestinal flora of patients with CRF complicated with CHD and their relationship with ASI to understand the association of those changes and ASI with CRF comorbid with CHD, with the goal of offering a reliable clinical basis for active prevention and treatment of CRF and CHD in the future. Design center dot The research team designed a prospective controlled study. Setting center dot The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei, China. Participants center dot Participants were 86 patients with both CRF and CHD and 72 patients with CHD only who had been admitted to the hospital between October 2019 and January 2021. Intervention center dot The intervention group included participants who had received a diagnosis of CRF complicated with CHD and the control group included participants who had received a diagnosis of CHD only. Outcome Measures center dot The research team counted participants' intestinal flora and measured their ambulatory blood pressure and arterial stiffness index (ASI) to analyze the correlation of the ASI with the intestinal flora and the related factors impacting CHD in patients with CRF. Results center dot The monitoring of participants' ambulatory blood pressures showed that the intervention group's day systolic blood pressure (dSBP) and 24h SBP were significantly higher, while the group's day diastolic blood pressure (dDBP) and 24h DBP were significantly lower than those of the control group. The intervention group's levels of lactobacillus, bacteroidaceae, and bifidobacterium were significantly lower than those of the control group, and those intestinal flora were negatively correlated with ASI. The intervention group's levels of Escherichia coli and yeasts were significantly higher than those of the control group, and those intestinal flora were positively correlated with ASI. A significant relationship existed between lactobacillus and yeast and the occurrence of CHD in the CRF participants. Conclusions center dot Patients with both CRF and CHD have an obvious intestinal-flora imbalance, and the imbalance is strongly bound up with their ASI, which is of great reference significance for novel therapy of such patients and for the clinical application of ASI. (Altern Ther Health Med. 2023;29(1):252-257).