: 8–13  Hippocrates referred to the use of salicylic tea to reduce fevers around 400 BC, and willow bark preparations were part of the pharmacopoeia of Western medicine in classical antiquity and the Middle Ages. Willow bark extract became recognized for its specific effects on fever, pain, and inflammation in the mid-eighteenth century. By the nineteenth century, pharmacists were experimenting with and prescribing a variety of chemicals related to salicylic acid, the active component of willow extract. : 46–55 

In 1853, chemist Charles Frédéric Gerhardt treated sodium salicylate with acetyl chloride to produce acetylsalicylic acid for the first time;: 46–48  in the second half of the 19th century, other academic chemists established the compounds chemical structure and devised more efficient methods of synthesis. In 1897, scientists at the drug and dye firm Bayer began investigating acetylsalicylic acid as a less-irritating replacement for standard common salicylate medicines, and identified a new way to synthesize it. : 69–75  By 1899, Bayer had dubbed this drug Aspirin and was selling it globally. : 27  The word Aspirin was Bayers brand name, rather than the generic name of the drug; however, Bayers rights to the trademark were lost or sold in many countries. Aspirins popularity grew over the first half of the 20th century leading to fierce competition with the proliferation of aspirin brands and products.Aspirins popularity declined after the development of acetaminophen/paracetamol in 1956 and ibuprofen in 1962.
In the 1960s and 1970s, John Vane and others discovered the basic mechanism of aspirins effects,: 226–231  while clinical trials and other studies from the 1960s to the 1980s established aspirins efficacy as an anti-clotting agent that reduces the risk of clotting diseases. : 247–257  The initial large studies on the use of low-dose aspirin to prevent heart attacks that were published in the 1970s and 1980s helped spur reform in clinical research ethics and guidelines for human subject research and US federal law, and are often cited as examples of clinical trials that included only men, but from which people drew general conclusions that did not hold true for women.Aspirin sales revived considerably in the last decades of the 20th century, and remain strong in the 21st century with widespread use as a preventive treatment for heart attacks and strokes. : 267–269

Trademark
Bayer lost its trademark for Aspirin in the United States in actions taken between 1918 and 1921 because it had failed to use the name for its own product correctly and had for years allowed the use of "Aspirin" by other manufacturers without defending the intellectual property rights. Today, aspirin is a generic trademark in many countries. Aspirin, with a capital "A", remains a registered trademark of Bayer in Germany, Canada, Mexico, and in over 80 other countries, for acetylsalicylic acid in all markets, but using different packaging and physical aspects for each.