He was one of the first pupils at Ampleforth College. He began his schooling in 1804 shortly after the monks, in exile from France, settled in the lodge of Anne Fairfax's chaplain in the Ampleforth Valley. He went on from Ampleforth in 1810 to Edinburgh University, where he received his degree as a doctor of medicine on August 1, 1815 at the age of 19. In 1816 he entered Lord Byron's service as his personal physician.
In 1816, Doctor Polidori accompanied Byron on a trip through Europe. In Geneva, Switzerland, the pair met with Mary Wollstonecraft Shelley, and her husband Percy Bysshe Shelley, and their companion Clair Clairmont. One night in June, after the company had read aloud from a collection of horror tales, Byron suggested that they each write a ghost story. Mary Shelley worked on a tale that would later evolve into Frankenstein. Byron wrote (and quickly abandoned) a fragment of a story, which Polidori used later as inspiration for his own tale.
Rather than use the crude, bestial vampire of folklore as a basis for his story, Polidori based his character on Byron. Polidori named the character "Lord Ruthven" as a joke. The name was originally used in Lady Caroline Lamb's novel Glenarvon, in which a thinly-disguised Byron figure was also named Lord Ruthven. Polidori's Lord Ruthven was not only the first vampire in English fiction, but was the first fictional vampire in the form we recognize today - an aristocratic fiend who preyed among high society.
Polidori's story, The Vampyre, was published in the April 1819 issue of New Monthly Magazine. Much to both his and Byron's chagrin, The Vampyre was released as a new work by Byron. Byron even released his own Fragment of a Novel in an attempt to clear up the mess, but, for better or worse, The Vampyre continued to be attributed to him.
Dismissed by Byron, Polidori returned to England, and in 1820 wrote to the Prior at Ampleforth; his letter is lost, but Prior Burgess' reply makes it clear that he considered Polidori, with his scandalous literary acquaintances, an unsuitable case for the monastic profession. After writing an ambitious sacred poem, The Fall of the Angels, in 1821, Polidori, suffering from depression, died in mysterious circumstances on August 24, 1821 at approximately 1:10 PM, probably by self-administered poison, though the coroner's verdict was that he had "departed this Life in a natural way by the visitation of God".
Polidori's fate has been to be remembered only as a footnote in Romantic history. Reprints of the diary he kept during his travels with Byron are available, but are rather hard to find for purchase on the internet, and no etext version is yet available.
Polidori's diary, titled The Diary of John Polidori and edited by William Michael Rossetti, was first published in 1911 by Elkin Mathew (London). A reprint of this book, The diary of Dr. John William Polidori, 1816, relating to Byron, Shelley, etc was published by Folcroft Library Editions (Folcroft, Pa.) in 1975. Another reprint by the same title was printed by Norwood Editions (Norwood, Pa.) in 1978.