US researchers found nearly one out of every 25 people aged 57 to 85 took dangerous combinations of drugs with the potential for serious interactions, the study found.
For men ages 75 to 85, it was as high as 1 in 10.
"The public has an awareness that two prescription medications used together might be dangerous," said study author Stacy Tessler Lindau of the University of Chicago Medical Center.
"But what people don't fully appreciate is that non-prescription drugs can interact with prescription drugs and even other non-prescription drugs."
About a third of older adults uses five or more prescriptions and about half use over the counter medications and dietary supplements, the study found.
More than half of older adults used five or more prescription medications, over-the-counter medications or dietary supplements while 29 percent took more than five prescription medications.
More than half of the dangerous drug combinations included the use of aspirin or blood thinners such as warfarin.
The most common dangerous combination of non-prescription drugs was ginkgo biloba and aspirin which can increase the risk of internal bleeding when taken together.
Researchers at the University of Chicago studied the medication use of 3,500 people aged 57 to 85 living independently across the United States to create a representative sample.
When extrapolated to the general population, the study found that some 2.2 million people were at risk from dangerous combinations of medications.
A recent report found that US adults over the age of 65 make are taken to the emergency room more than 175,000 times every year because of bad reactions to medication.
The study was published in this week's edition of the Journal of the American Medical Association.