Discriminating acute respiratory distress syndrome (ARDS) from acute cardiogenic pulmonary edema (CPE) may be challenging in critically ill patients. Aim of this study was to investigate if gray-level co-occurrence matrix (GLCM) analysis of lung ultrasound (LUS) images can differentiate ARDS from CPE. The study population consisted of critically ill patients admitted to intensive care unit (ICU) with acute respiratory failure and submitted to LUS and extravascular lung water monitoring, and of a healthy control group (HCG). A digital analysis of pleural line and subpleural space, based on the GLCM with second order statistical texture analysis, was tested. We prospectively evaluated 47 subjects: 16 with a clinical diagnosis of CPE, 8 of ARDS, and 23 healthy subjects. By comparing ARDS and CPE patients’ subgroups with HCG, the one-way ANOVA models found a statistical significance in 9 out of 11 GLCM textural features. Post-hoc pairwise comparisons found statistical significance within each matrix feature for ARDS vs. CPE and CPE vs. HCG (P ≤ 0.001 for all). For ARDS vs. HCG a statistical significance occurred only in two matrix features (correlation: P = 0.005; homogeneity: P = 0.048). The quantitative method proposed has shown high diagnostic accuracy in differentiating normal lung from ARDS or CPE, and good diagnostic accuracy in differentiating CPE and ARDS. Gray-level co-occurrence matrix analysis of LUS images has the potential to aid pulmonary edemas differential diagnosis.