Creating search strategies for systematic reviews, finding the best balance between sensitivity and specificity, and translating search strategies between databases is challenging. Several methods describe standards for systematic search strategies, but a consistent approach for creating an exhaustive search strategy has not yet been fully described in enough detail to be fully replicable. The authors have established a method that describes step by step the process of developing a systematic search strategy as needed in the systematic review. This method describes how single-line search strategies can be prepared in a text document by typing search syntax (such as field codes, parentheses, and Boolean operators) before copying and pasting search terms (keywords and free-text synonyms) that are found in the thesaurus. To help ensure term completeness, we developed a novel optimization technique that is mainly based on comparing the results retrieved by thesaurus terms with those retrieved by the free-text search words to identify potentially relevant candidate search terms. Macros in Microsoft Word have been developed to convert syntaxes between databases and interfaces almost automatically. This method helps information specialists in developing librarian-mediated searches for systematic reviews as well as medical and health care practitioners who are searching for evidence to answer clinical questions. The described method can be used to create complex and comprehensive search strategies for different databases and interfaces, such as those that are needed when searching for relevant references for systematic reviews, and will assist both information specialists and practitioners when they are searching the biomedical literature.