Older adults commonly use over-the-counter medications and dietary supplements, which can lead to adverse events when taken alone and in combination with prescription medications. Since older patients are typically prescribed more medications, they are at higher risk for adverse effects from supplements and over-the-counter drugs. This population-based sample of adults between ages 62 and 85 found that while the use of over-the-counter medications declined over time, the number of dietary supplements and prescribed medications increased. Specific medication classes and dietary supplements with the potential for harmful interactions were frequently used. About 15% of participants were at risk for a major drug–drug interaction, demonstrating the need to systematically address medication and supplement safety in older adults.