Objectives <p>Coronary heart disease (CHD) stands as a major cause of fatal outcomes, but current diagnostic methods often lack sensitivity or are highly invasive. The synergistic role of miR-193a-5p and VEGFB in CHD remains unclear. This study explores their combined predictive value for CHD diagnosis and prognosis.</p> Methods <p>105 CHD and 70 non-CHD subjects were enrolled. Serum was collected to detect the abundance of miR-193a-5p and VEGFB. The diagnostic efficacy of the two was analyzed by ROC curve. The prognosis was recorded during the follow-up, and risk factors were evaluated of CHD occurrence and prognosis by logistic regression.</p> Results <p>In the serum of CHD patients, the abundance of miR-193a-5p was down-regulated, while VEGFB was up-regulated, and their expressions were significantly correlated. The AUC of miR-193a-5p and VEGFB for individual diagnosis of CHD was 0.9097 and 0.7512, which increased to 0.9415 for combined diagnosis. In the poor prognosis group, miR-193a-5p was lower and VEGFB was higher. The AUC of their combined prediction for poor prognosis was 0.9575, significantly better than individual detection. Logistic regression showed that miR-193a-5p and VEGFB were independent influencing factors for CHD occurrence and poor prognosis.</p> Conclusion <p>miR-193a-5p combined with VEGFB has high value for the diagnosis and prognostic evaluation of CHD, and is expected to become a new biomarker and potential therapeutic target for precision diagnosis and treatment of CHD.</p>