OBJECTIVES:  (1) To characterize changes in the prevalence of medication use, including concurrent use of prescription and over-the-counter medications and dietary supplements; and (2) to quantify the frequency and types of potential major drug-drug interactions. METHODS: Descriptive analyses of a longitudinal, nationally-representative sample of community-dwelling older adults aged 62 through 85 years. In-home interviews with direct medication inspection were conducted in 2005-2006 (N=2,351) and again in 2010-2011 (N=2,206). We defined medication use as the use of at least one prescription or over-the-counter medication or dietary supplement at least daily or weekly and concurrent use as the regular use of at least two medications. We used Micromedex to identify potential major drug-drug interactions. RESULTS: Use of at least 1 prescription medication slightly increased from 84.1% in 2005-2006 to 87.7% in 2010-2011 (p<0.05). The concurrent use of at least 5 prescription medications increased from 30.6% to 35.8% (p<0.001). While the use of over-the-counter medications declined from 44.4% to 37.9%, the use of dietary supplements increased from 51.8% to 63.7% (all p values<0.001). There were clinically significant increases in the use of statins (33.8% to 46.2%), anti-platelets (32.8% to 43.0%), and omega-3 fish oils (4.7% to 18.6%) (all p-values <0.05). In 2010-2011, 15.1% of older adults were at risk of a potential major drug-drug interaction, compared to 8.4% in 2005-2006 (p<0.001). The vast majority of these interacting regimens involved medications and dietary supplements increasingly used in 2010-2011. CONCLUSIONS: Use of prescription medications and dietary supplements, and the concurrent use of interacting medications, has increased since 2005, with nearly 1 in 6 older adults potentially at risk for a major drug-drug interaction. Improving safety when using multiple medications has the potential to reduce preventable adverse drug events associated with medications commonly used among older adults.