OBJECTIVES: To quantify and characterize economic-content in pharmaceutical advertisements, and its supporting evidence, in leading American medical journals from 1990-2006. METHODS: Two researchers reviewed all pharmaceutical advertisements in three leading general medical (New England Journal of Medicine, JAMA, and Annals of Internal Medicine) and specialty journals (Circulation, Gastroenterology, Neurology) in three specified months each year for 2000 through 2006. Using a standardized data collection form, we investigated economic claims (e.g., ads using the words “value”, “price”, “savings”, “hospitalization,” etc.), as well as the supporting evidence. This work builds upon our previous research of economic claims from 1990-1999, adding new data and content. RESULTS: We reviewed 3,516 pharmaceutical advertisements (2144 from 1990-1999 and 1372 from 2000-2006). Economic content occurred in 11.1% of ads in the 1990s, and 7.6% of ads in 2000-2006 (p=0.0007). From 1997 to 2002, economic advertisements declined (p<0.0001), and increased again from 2003-2006 (p=0.0006), with a peak in 1997 at 16.2% and a nadir of 3.9% in 2002. Economic claims appeared with similar frequency in the specialty journal ads across time periods (1990s: 8.6% vs. 2000-2006: 8.5%; p=0.91), but declined in the general medical journal ads (1990s: 13.0% vs. 2000-2006: 6.4%; p<0.0001). The presence of supporting evidence for economic claims was similar in the 1990s and 2000s (63.7% vs. 61.5%, p=0.70), but over time derived less from the Red Book (1990s: 38.7% vs. 2000-2006: 15.6%) and average wholesale price listings (1990s: 51.1% vs. 2000-2006: 6.3%) and more from data on file (1990s: 9.5% vs. 2000-2006: 29.7%) and published studies (1990s: 6.6% vs. 2000-2006: 23.4%). From 2000-06, a small number of ads mentioned patient compliance (2.6%) or persistence (2.0%). CONCLUSION: Drug companies continue to promote health economic messages in medical journal advertisements. Mention of supporting evidence underlying economic claims has not changed over time, though more ads reference published studies.