ObjectiveClinical decision support systems (CDSS) have a critical role in improving the quality and safety of health care delivery. CDSS rules direct the behavior of CDSS. However, the CDSS rules have not been routinely shared and reused, and ontology can promote the reusing of CDSS rules. We systematically screened literature to elaborate on the current status of ontology applied in CDSS rule management.MethodsWe searched PubMed, the Association for Computing Machinery (ACM) Digital Library, and the Nursing & Allied Health Database for publications focusing on ontology, clinical decision support, and rules. Grounded theory and PRISMA 2020 guidelines were followed. One author started the screening and literature analysis, and two authors validated the processes and results. Inclusion and exclusion criteria were developed and refined iteratively.ResultsAmong 81 included publications, the identified CDSS were mainly applied to managing chronic conditions, alerts for medication prescriptions, reminders for immunizations and preventive services, diagnoses, and treatment recommendations. The CDSS rules were presented in Semantic Web Rule Language, Jess, or Jena formats. Despite ontology was used to supply medical knowledge, CDSS rules, and terminologies to CDSS, ontology has not been used in CDSS rule management.ConclusionsAlthough ontology can facilitate the reuse, management, and maintenance of CDSS rules, CDSS ontology remains unavailable indicating that more efforts are needed to improve the reusability and interoperability of CDSS rules.