Introduction Shortness of breath is a leading cause of intensive care unit (ICU) admissions and is multifactorial. Acute hypoxemic respiratory failure due to heart failure is one of the leading causes of ICU admissions. N-terminal pro-brain natriuretic peptide (NT-proBNP) is secreted by ventricles and carries a negative predictive value for heart failure (2). NT-proBNP can also be raised in sepsis (4). Changes in NT-proBNP strongly correlated with changes in C-reactive protein (CRP) and leukocytes levels (8). Objective This study was conducted to explore the diagnostic utility of NT-proBNP and CRP to diagnose heart failure in patients presenting with acute hypoxemic respiratory failure. Materials and methods After informed consent and approval from the institutional review board (IRB), patients of acute hypoxemic respiratory failure were included in the study. History and physical examination were done by a medical resident and recorded in the patients’ files. Data were transferred to a structured proforma by the researcher. All tests were conducted within three hours of presentation. The diagnosis of heart failure was made by a panel of experts, including the consultant cardiologist and consultant intensivist in charge. The chest X-ray was reported by the radiologist. The cost of the test was afforded by the institution. Data were analyzed by SPSS version 15 (SPSS Inc., Chicago, Illinois). Analysis of variance (ANOVA), Pearson correlation and linear regression were applied to find out the relation between variables and significance. Results We studied 137 patients. Out of them, 72.9% were diagnosed as heart failure. Heart failure was more common in females (43.7%) as compared to males (29%). NT-proBNP was raised in 111 (81%) patients and out of them, 88 patients (79%) had heart failure. Sensitivity and specificity of NT-proBNP were found to be (95.56%) and (46.81%), respectively. Similarly, CRP was 90% sensitive and 25.53% specific for heart failure. The most common findings in chest X-rays of patients with heart failure were upper lobe diversion and enlarged cardiothoracic ratio (71%). Conclusion We concluded our study as NT-proBNP is a highly sensitive test to diagnose heart failure in settings of acute hypoxemic respiratory failure. CRP is also significantly raised in heart failure. Upper lobe diversion and an increased cardiothoracic ratio is a strong predictor of heart failure.Copyright © 2020, Abdullah et al.