Inclusion Criteria:
-Meets the definition of nonintubated ARDS per the 2024 Global Definition of ARDS that includes all the following (2A-2D):
* 2A. Risk factors and origin of pulmonary edema: Precipitated by an acute predisposing risk factor, specifically from a suspected pathogen-associated etiology such as pneumonia\* or non-pulmonary infection\*\* \[\*Pneumonia defined as known or suspected based on treating physician documentation or discussion, OR both of the following criteria: 1) Chest radiography with new infiltrates, consolidation, or cavitation and (2) Clinical signs of pneumonia (new cough, sputum, fever, or white blood cells (WBC) \> 12,000)\] \[\*\*Non-pulmonary infection defined as suspected or proven infection meeting any of the following criteria: treating clinician suspects a viral, bacterial, or fungal infection, or cultures ordered in the past 24h or positive cultures within 1 week; or orders for antimicrobial medication.\]
* 2B. Oxygenation: PaO2:FIO2 ≤ 300 mm Hg or SpO2:FIO2 ≤ 315 (if SpO2 ≤ 97%) on High-Flow Nasal Oxygen (HFNO) with flow of ≥ 30 L/min or non-invasive ventilation (NIV)/continuous positive airway pressure (CPAP) with at least 5 cm H2O end-expiratory pressure
* 2C. Timing: Acute onset or worsening of hypoxemic respiratory failure within 1 week of the estimated onset of the predisposing risk factor or new or worsening respiratory symptoms.
* 2D. Chest imaging: Chest infiltrates on radiography and computed tomography or B lines and/or consolidations on ultrasound not fully explained by effusions, atelectasis, or nodules/masses.
Exclusion Criteria:
* Hypersensitivity to vadadustat or any of its excipients
* Placed on mechanical ventilation before randomization
* Patients on home oxygen therapy
* Time since hospital admission order placed \>72 hours
* Hemoglobin above the gender-specific upper limit of normal (ULN) at randomization: 16 grams/deciliter (g/dL) for females and 18 g/dL for males
* Patients with Aspartate transferase (AST) or Alanine aminotransferase (ALT) levels \>5 times the upper limit of normal
* Patients with AST or ALT levels \>3 times the upper limit of normal along with a total bilirubin elevation of \>2 times the upper limit of normal.
* Patients who have erythrocytosis or polycythemia vera
* Patients with uncontrolled hypertension
* Patients with active malignancy
* Patients with liver cirrhosis or active, acute liver disease
* Patients taking erythropoiesis-stimulating agents
* Patient taking probenecid, rifampicin, gemfibrozil, or teriflunomide
* Women who are pregnant or breastfeeding, or positive pregnancy test before randomization
* Patients who are prisoners
* Patients who are currently enrolled in any other interventional clinical trial
* Patients who have any prior history of arterial or venous thromboembolism within the past 3 months
* Patients with a history of myocardial infarction, cerebrovascular event, or acute coronary syndrome within the past 3 months
* Patients with known or suspected tuberculosis infection
* Moribund patient not expected to survive 48 hours