OBJECTIVES: To describe the growth over time and methodological quality of cost-utility analyses (CUAs) published in the peer-reviewed literature through 2006. METHODS: This study updates and expands our previous work, which examined CUAs through 2003 (n=795). We systematically searched the English-language literature for original CUAs published through 2006 using Medline and other databases. Two trained readers independently audited each study and collected data on a wide variety of elements related to study origin, methods, and reporting of results. RESULTS: We identified 1431 original CUAs (currently included in the Tufts Medical Center Cost-Effectiveness Analysis Registry, www.cearegistry.org). The more than 200 CUAs published annually from 2004 to 2006 nearly doubled the size of the CUA literature. Most analyses pertain to the U.S. (51%), followed by the U.K. (16%), and Canada (7%). CUAs cover a wide range of disease areas, including cardiovascular diseases (15%), infectious diseases (14%), and cancer (13%), and examine interventions for tertiary care (62%), secondary prevention (23%), and primary prevention (15%). Although most studies adhere to guidelines for conducting and reporting CUA results, their average quality (4.2±1.1 on a 1-7 Likert scale) did not change substantially over time. Study quality was higher for CUAs published in experienced journals (publishing a total of ≥10 CUAs); (n=31 journals), vs. other (n=390 journals); (4.5±1.1 vs. 3.9±1.1, respectively; p<0.0001), for CUAs evaluating pharmaceuticals vs. other interventions (4.3±1.0 vs. 4.1±1.2, respectively; p<0.0001), and for CUAs supported by a government organization vs. other sponsors (4.4±1.0 vs. 4.1±1.2, respectively; p<0.0001). CONCLUSIONS: The rapid growth in published CUAs demonstrates the increased role these analyses play in informing resource allocation decisions. Journals should conduct more rigorous reviews and assure adherence to guidelines for conducting and reporting CUA results.