OBJECTIVES: The aim of this study was to evaluate trends in the use of herbs and dietary supplements (HDS) in relation to prescription drug (Rx) use, as well as their individual use, among US adults from 1999-2004. METHODS: Data were abstracted from the 1999-2000 and 2003-2004 cycles of the National Health and Nutrition Examination Survey (NHANES). HDS included herbs, vitamins, minerals, and other supplements. Trends in HDS and/or Rx use were examined based on stratified characteristics (i.e., sociodemographics, insurance coverage, healthcare visits during the preceding year, chronic conditions). Sampling weights were adjusted to allow for the pooling of data from multiple waves. RESULTS: Overall, the proportion of HDS users increased from 51.2% during 1999-2000 to 53.0% during 2003-2004, while that of Rx users increased from 49.9% to 55.6% over the same period. Between 1999 and 2004, the proportion of HDS-only users decreased while the proportion of people who only used Rx increased. The concomitant use of HDS and Rx increased for most subgroups, except for those who had an annual household income less than $ 14,999 or greater than $65,000, and who had never have healthcare visits during the preceding year. CONCLUSIONS: Trends suggest that concomitant HDS and Rx use increased over the period of observation in the general US population. Further research is needed to investigate the outcomes of concurrent HDS and Rx use.