Document clustering has been used for better document retrieval, document browsing, and text mining in digital library. In this paper, we perform a comprehensive comparison study of various document clustering approaches such as three hierarchical methods (single-link, complete-link, and complete link), Bisecting K-means, K-means, and Suffix Tree Clustering in terms of the efficiency, the effectiveness, and the scalability. In addition, we apply a domain ontology to document clustering to investigate if the ontology such as MeSH improves clustering qualify for MEDLINE articles. Because an ontology is a formal, explicit specification of a shared conceptualization for a domain of interest, the use of ontologies is a natural way to solve traditional information retrieval problems such as synonym/hypernym/ hyponym problems. We conducted fairly extensive experiments based on different evaluation metrics such as misclassification index, F-measure, cluster purity, and Entropy on very large a...