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Objective Clinical pathways (CPs) are widely studied methods to standardize clinical intervention and improve medical quality. However, standard care plans defined in current CPs are too general to execute in a practical healthcare environment. The purpose of this study was to create hospital-specific personalized CPs by explicitly expressing and replenishing the general knowledge of CPs by applying semantic analysis and reasoning to historical clinical data. Methods A semantic data model was constructed to semantically store clinical data. After querying semantic clinical data, treatment procedures were extracted. Four properties were self-defined for local ontology construction and semantic transformation, and three Jena rules were proposed to achieve error correction and pathway order recognition. Semantic reasoning was utilized to establish the relationship between data orders and pathway orders. Results A clinical pathway for deviated nasal septum was used as an example to illustrate how to combine standard care plans and practical treatment procedures. A group of 224 patients with 11,473 orders was transformed to a semantic data model, which was stored in RDF format. Long term order processing and error correction made the treatment procedures more consistent with clinical practice. The percentage of each pathway order with different probabilities was calculated to declare the commonality between the standard care plans and practical treatment procedures. Detailed treatment procedures with pathway orders, deduced pathway orders, and orders with probability greater than 80% were provided to efficiently customize the CPs. Conclusions This study contributes to the practical application of pathway specifications recommended by the Ministry of Health of China and provides a generic framework for the hospital-specific customization of standard care plans defined by CPs or clinical guidelines. [ABSTRACT FROM AUTHOR]