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Managing patients with respiratory failure increasingly involves non-invasive respiratory support (NIRS) strategies to support respiration, often preventing the need for invasive mechanical ventilation. However, despite the rapidly expanding use of NIRS, there remains a significant challenge to its optimal use across all medical circumstances. It lacks a unified ontological structure, complicating guidance on NIRS modalities across healthcare systems. In this study, we introduced NIRS ontology to support knowledge representation in acute care settings by providing a unified framework that enhances data clarity and interoperability, laying the groundwork for future clinical decision-making research. We developed NIRS ontology using the Web Ontology Language (OWL) and Protégé to organize clinical concepts and relationships. To enable rule-based clinical reasoning beyond hierarchical structures, we added Semantic Web Rule Language (SWRL) rules. We evaluated logical reasoning using a sample of 6 patient scenarios and used SPARQL queries to retrieve and test targeted inferences. The ontology has 145 classes, 11 object properties, and 18 data properties across 949 axioms that establish concept relationships. To standardize clinical concepts, we added 392 annotations, including descriptive definitions based on controlled vocabularies. SPARQL queries successfully validated all test cases (rules) by retrieving appropriate patients' outcomes: for instance, a patient treated with HFNC (high-flow nasal cannula) for 2 hours due to acute respiratory failure may avoid endotracheal intubation. This NIRS ontology formally represents domain-specific concepts, including ventilation modalities, patient characteristics, therapy parameters, and outcomes. SPARQL query evaluations across clinical scenarios confirmed the ontology's ability to support rule‑based reasoning and therapy recommendations, providing a foundation for consistent documentation practices, integration into clinical data models, and advanced analysis of NIRS outcomes. In conclusion, this proof-of-concept NIRS ontology demonstrates how clinical concepts can be formally represented and queried, offering a foundation for future validation, EHR integration, and evidence-based refinement of NIRS practices.