OBJECTIVES: Health economic researchers use electronic databases to review current and ancestral literature across therapy areas.  In the United States and Canada, researchers tend to use MEDLINE, and in other parts of the world EMBASE is the literature database of choice.  EMBASE is fee-based and MEDLINE is available gratis through the National Library of Medicine.  Using the search engine OVID, both databases can be searched simultaneously, with a paid subscription.  MEDLINE indexes 5600 journals and EMBASE indexes 7600 journals; all MEDLINE records are included in EMBASE.  EMBASE also includes conference abstracts which MEDLINE does not. Additionally, EMBASE assigns more index terms to references than MEDLINE which can result in less focused searches. The researchers were interested in comparing and contrasting search results in both databases, particularly in the area of health economics. METHODS: Researchers selected three broad search terms: cost of illness (COI), burden of illness (BOI) and cost benefit analysis (CBA) that would be recognized in both databases.  Each search was run with chronic pulmonary obstructive disease as the treatment focus, 2010-2011, English only. RESULTS: The results were unexpectedly mixed. In the area of CBA, MEDLINE generated a higher number of references, 30 versus 17 in EMBASE with 11 duplicated records.  COI and BOI searches resulted in a larger number of citations for EMBASE, 11 and 149, versus 7 and 105 for MEDLINE with 6 and 101 duplicates, respectively.    Conference abstracts accounted for the higher number of hits in EMBASE over MEDLINE. CONCLUSIONS: Health economic researchers rely on the most up-to-date information to identify cost and treatment trends and the inclusion of conference abstracts in EMBASE support conducting these searches using both databases, particularly for systematic literature reviews where use of EMBASE could be a requirement. Further examination into the nuances of search terms and indexing in both databases is warranted.