Introduction. In the United States, dietary supplement (DS) use is common, often takes place outside of the purview of health care providers, and may involve DS in combination with pharmaceuticals. This situation has led to concerns about interactions between DS and pharmaceuticals, as well as the risks from polypharmacy and polysupplement use. Methods. We used data from the Midlife in the US study (MIDUS 2 Survey) to examine DS and prescription pharmaceutical use in 3876 study participants in order to determine the demographics of high-users (5 or more) of DS and pharmaceuticals and the presence of DS-pharmaceutical co-use. Results. Over 69% of study participants regularly used DS, 49.6% regularly used both DS and pharmaceuticals, and 6.3% and 8.7% were high-users of pharmaceuticals and DS, respectively. High-users of DS, pharmaceuticals, and either were more likely than the whole cohort to be female and of lower income. Conclusions. These findings corroborate those of other national studies with respect to the demographics of DS users but add new information about people at risk of DS-pharmaceutical interactions, not an insignificant proportion of the population examined by this dataset.