Objective To investigate the value of intravascular ultrasound (IVUS) parameters combined with microRNA-206 (miR-206) in assessing the severity and prognosis of non-ST-elevation acute myocardial infarction (NSTEAMI).Methods The 105 NSTEAMI patients admitted to our hospital from March 2019 to April 2021 were selected. All patients underwent percutaneous coronary intervention (PCI) and were divided into single-vessel disease group (n = 55), double-vessel disease group (n = 32) and multi-vessel disease group (n = 18) according to the lesion severity. IVUS parameters and serum levels of miR-206 were compared among patients with different degrees of the lesion severity, and the correlations of IVUS parameters and serum levels of miR-206 levels with the lesion severity was analyzed in NSTEAMI patients. Patients were followed up for 2 years, and were further divided into the occurrence group and the non-occurrence group according to whether they had major adverse cardiac events (MACE). The clinical data of patients in the occurrence group and the non-occurrence group were compared. Multivariable Logistic regression analysis was performed to determine the factors affecting the occurrence of MACE in NSTEAMI patients. The receiver operating characteristic (ROC) curve was plotted to assess the predictive value of IVUS parameters and serum miR-206 for MACE in NSTEAMI patients.Results The plaque load, plaque area, remodeling index, eccentricity index and the serum level of miR-206 in the multi-vessel disease group were higher than those in the single-vessel disease group and the double-vessel disease group (P < 0.05), and those in the double-vessel disease group were even higher than those in the single-vessel disease group (P < 0.05). The Pearson correlation analysis revealed that there was no correlation between the external elastic membrane area and the lesion severity in NSTEAMI patients (r =0.271, P =0.325), and that the plaque load, plaque area, remodeling index, eccentricity index, and the serum level of miR-206 were positively correlated with the lesion severity in NSTEAMI patients (r = 0.416, 0.382, 0.423, 0.507 and 0.394, all P = 0.000). After two years of follow-up, 2 cases were lost. Among the rest 103 patients, 32 (31.068%) had MACE and 71 (68.932%) did not. The proportions of multi-vessel disease and myocardial revascularization failure, plaque load, plaque area, remodeling index, eccentricity index and the serum level of miR-206 in the occurrence group were higher than those in the non-occurrence group (P < 0.05), and the lymphocyte count and the level of hemoglobin in the occurrence group were lower than those in the non-occurrence group (P < 0.05). Multivariable Logistic regression analysis showed that multi-vessel disease [O^R = 3.466 (95% CI: 1.523, 7.884) ], myocardial revascularization failure [O^R = 2.776 (95% CI: 1.220, 6.315) ], high plaque load [O^R = 3.155 (95% CI: 1.387, 7.177) ], high remodeling index [O^R = 3.842 (95% CI: 1.689, 8.740) ], high eccentricity index [O^R = 4.166 (95% CI: 1.831, 9.477) ], and high serum level of miR-206 [O^R = 4.500 (95% CI: 1.978, 10.236) ] were risk factors for MACE in NSTEAMI patients (P < 0.05). ROC curve analysis demonstrated that the sensitivity of the combined detection of plaque load, remodeling index, eccentricity index and the serum level of miR-206 for predicting the occurrence of MACE in NSTEAMI patients was 88.52% (95% CI: 0.674, 0.957), with the specificity being 92.86% (95% CI: 0.713, 0.968) and the area under curve being 0.900 (95% CI: 0.812, 0.953) (P < 0.05).Conclusion IVUS parameters (plaque load, remodeling index, eccentricity index) and serum miR-206 are of great value in assessing the severity and prognosis of NSTEAMI patients, and the combination of the four exhibits a higher predictive value.