The success of any organization is highly dependent on choosing the right strategic orientation. The main objectives of the present study were to identify appropriate knowledge management strategies and their subsystems in the libraries of Iranian universities of medical science, and to examine their level of strategic alignment. The study population consisted of 55 managers and 225 librarians working at 33 central libraries in Iranian universities of medical science. In order to carry out the research, two questionnaires were initially designed to collect information about the dominant system strategies and knowledge management subsystems. Then, the means of the sum of the items that were planned for each strategy were calculated, the highest means in each group were considered as the basis for determining the dominant strategy, and the levels of alignment between the different strategies were assessed. The results showed that, with regard to the degree of dynamism, maintaining the status quo was the dominant strategy of the knowledge management system in the selected academic libraries, and with regard to the knowledge acquisition and identification subsystem, passive was the dominant strategy. Externalization was the dominant strategy related to the knowledge creation and transfer subsystem, and static was the dominant strategy related to the knowledge application subsystem. As for the level of alignment between the strategies, the results revealed that the strategic alignment is at an average level. Based on the findings, improving the existing conditions in these libraries requires a transition from traditional knowledge management approaches towards more modern approaches, as well as the selection of optimal implementation strategies for the knowledge management system and subsystems.