Objective To evaluate the relationship between sublingual microcirculation differences and weaning success rate and prognosis in elderly patients with severe pneumonia. Methods A retrospective observation cohort study was conducted. Forty-two elderly patients with severe pneumonia who underwent mechanical ventilation in the intensive care unit of Sir Run Run Hospital, Nanjing Medical University from February 2022 to August 2022 were recruited in the study. They were divided into a high-flow nasal cannula oxygen group (HFNC group, n=33) and a non-invasive positive pressure ventilation group (NIPPV group, n=9) according to the mode of post-weaning ventilation. The differences of N-terminal brain natriuretic peptide precursor (NT-proBNP), cardiac index (CI) and sublingual microcirculation indexes between the two groups were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of each parameter on weaning success rate and case fatality rate. Results Compared with the NIPPV group, CI, propotion of perfused vessels (PPV) and perfused vessel density (PVD) were higher, and NT-proBNP and total vessel density (TVD) were lower in the HFNC group (all P<0.05). The prediction value of PPV combined with PVD was the largest, with area under the ROC curve (AUC) of 0.875, sensitivity of 75.8%, specificity of 88.9%. CI, NT-proBNP, CI combined with NT-proBNP, PPV, PVD all had predictive value. Compared with the death group, the survival group had higher CI, central venous-to-arterial carbon dioxide difference [P(v-a)CO2] and PPV. For the prediction value of weaning success, CI combined with NT-proBNP had the largest predictive value, with AUC of 0.919, sensitivity of 81.8%, specificity of 100.0%, followed by CI. NT-proBNP, PPV, PVD, PPV combined with PVD all had predictive value. Compared with the death group, the survival group had higher CI, P(v-a)CO2 and PPV (all P<0.05). For predictive value assessment of 28-day survival rate, CI plus PPV had the largest AUC of 0.875, with sensitivity of 69.4%, and specificity of 100.0%. CI, P(v-a)CO2 and PPV all have predictive value. Conclusions Both CI and PPV can be used as predictors of weaning success rate and survival rate. PPV combined with PVD is an ideal predictor of survival rate.