Abstract Background Early risk stratification is essential for in-hospital management of ST-segment–elevation myocardial infarction (STEMI). Development of acute heart failure and pulmonary edema is associated with poorer prognosis in this setting. Velocity–time integral (VTI) estimates stroke volume and cardiac output and has never been tested in acute coronary syndromes. Purpose Our aim was to evaluate the prognostic ability of a novel cardiothoracic ultrasound protocol for hemodynamic assessment with lung ultrasound (LUS) and VTI in patients with STEMI. Methods LUS and VTI were performed within 24h of admission for STEMI. LUS consisted of 8 scanning zones. A LUS combined with VTI (LUV) classification was developed. Receiver operating characteristic (ROC) analyses were performed to assess LUV score with in-hospital mortality, and it was compared with traditional Killip classification. Results From September 2022 and January 2023, 104 consecutive patients were admitted with ST-segment–elevation myocardial infarction. Fifteen patients were excluded from the analysis because were not assessed within 24h of admission. Therefore, 89 patients were included in the final analysis. Mean age was 62 years, 59% were male, 55% had hypertension, 32% had diabetes, 43% was anterior wall myocardial infarction and 16% had Killip 3 or 4 at admission. Overall in-hospital mortality was 7.9% and mortality across LUV categories were 0%, 0%, 8% and 50% for LUV A-D, respectively. A VTI ≥ 14 implied a negative predictive value for in-hospital mortality of 100%. The area under the ROC curve of LUV classification for in-hospital mortality was 0.92 (P=0.001), and Killip classification (0.85, P<0.001; P=0.48 for the difference between curves – Figure 1). Incidences of culprit vessel according to LUV categories are illustrated at Figure 2. There were no left main culprit vessel in our sample. The distribution of Cardiac Output (CO) and Cardiac index (CI) and Cardiac Power Output (CPO) were the following: LUV A: CO = 4.5 (1.2), CI = 4.0 (1.1) CPO = 0.9 (0.3); LUV B CO = 3.8 (0.9) CI = 3.4 (0.8) CPO = 0.7 (0.2); LUV C CO = 3.3 (0.8) CI = 3.0 (0.8) CPO = 0.6 (0.1) ; LUV D CO = 2.9 (0.7) CI = 2.7(0.5) CPO = 0.5(0.1). Conclusions In a cohort of patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention, LUV score provided an excellent AUC for prediction of in-hospital mortality. LUV score is an easy, noninvasive, rapidly acquired, and accurate method for risk stratification in STEMI patients.