Objective To evaluate the predictive value of inferior vena cava variability (△DIVC) for weaning failure before and after spontaneous breathing test (SBT) after mechanical ventilation in patients with respiratory failure and cardiac insufficiency. Methods From November 2016 to February 2018,0 patients with respiratory failure and cardiac insufficiency were included, who underwent mechanical ventilation in the ICU of Xuzhou Central Hospital of Jiangsu Province. The patients were divided into successful withdrawal (SW) group (n=62) who did not need tracheal intubation and non-invasive ventilator within 48 h after successful 30-min SBT and failed-withdrawal (FW) group (n=58) who needed reintubation or non-invasive ventilator 48 h after successful or failed 30-min SBT. Clinical characteristics and △DIVC of the two groups were recorded and compared before SBT and 30 min after SBT. SPSS statistics 17.0 was used for analysis. According to the data type, independent sample t test, Mann-Whitney U test or χ² test was used for comparison between groups. [JP+1]Multivariate logistic regression was used to analyze the risk factors for weaning failure, and the predictive value of △DIVC on weaning failure was analyzed using receiver operating characteristic(ROC)curve. Results There were significant differences between the 2 groups (P<0.05) in chronic respiratory disease, acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ), duration from the first intubation to extubation, and hemoglobin levels. The partial pressure of carbon dioxide and N-terminal pro-brain natriuretic peptide were significantly higher and left ventricular ejection fraction (LVEF) significantly lower in FW group than in SW group before and 30 min after SBT (P<0.05). At 30 min after SBT, the △DIVC in the FW group was significantly higher than that in the SW group (P<0.05). Multivariate logistic regression showed that LVEF (OR=1.204,5%CI 1.133-1.381; P=0.015) and △DIVC at 30 min after SBT (OR=1.450,5%CI 1.102-2.026; P=0.009) were independent risk factors for weaning failure. The area under ROC curve (AUC) for △DIVC was 0.905, and the best cut-off point was 0.27,2.4% for sensitivity and 94.4% for specificity. AUC for LVEF was 0.806, and the best cut-off point was 42.0%, 54.5% for sensitivity and 86.8% for specificity. Conclusion △DIVC at 30 min after SBT has a high predictive value for weaning failure in the patients with respiratory failure and cardiac disease.