Just 51 drugs - including painkillers and immune system-modifying agents - were responsible for the vast majority of reactions, new figures reveal.
In 2005 - the most recent year when figures have been made available - 15,107 people in America died as the result of taking a prescription drug, while 89,842 people suffered a serious adverse reaction, which resulted in disability, hospital care or a birth defect.
These reactions - all reported to America's drug regulator, the Food and Drug Administration - represent an increase of 2.7 times on figures produced in 1998.
Overall, the FDA received reports of 467,809 deaths and serious adverse reactions between 1998 and 2005.
(Source: Archives of Internal Medicine, 2007; 167: 1752-9).