In this paper, we present a semantic web based knowledge engineering approach to extend the coverage of medical knowledge-based systems in order to solve complex medical queries that demand the integration of deterministic and plausible knowledge. We leverage plausible reasoning mechanisms, which exploit associations between the underlying domain-specific data, as well as tentative domain knowledge, to extend the coverage of a medical knowledge base. We demonstrate that Semantic Web technologies, due to their efficient solutions for federated data management and built-in DL-based inferencing methods, offer useful opportunities to support plausible reasoning for medical decision support tasks. We evaluated our multi-strategy medical reasoning approach using real-world medical data. Our results illustrate that plausible reasoning improved the knowledge coverage of the original medical knowledge base by 10–12%, and in turn helped to solve complex disease diagnostic queries.