His most famous work is Curiositez inouyes sur la sculpture talismanique des Persans, horoscope des Patriarches et lecture des estoiles ("Unheard-of Curiosities concerning Talismanical Sculpture of the Persians, the horoscope of the Patriarchs, and the reading of the Stars), which was published in French in 1629 (and translated into English in 1650, by Edmund Chilmead). Jewish astrology developed independently from the mythology and star-gazing of the ancient Greek and Roman civilisations. Gaffarel included in his work two large folding plates of "the Celestial Constellations expressed by Hebrew characters", and asserted that the letters of the Hebrew alphabet could be interpreted from the constellations and that the heavens could be read as if a book.
The book enjoyed phenomenal success. René Descartes read this work with interest and the French physician and mathematician Pierre Gassendi (1592-1655) defended it. Unheard-of Curiosities was one of 1500 books in the Library of Sir Thomas Browne and one of the varied sources of his encyclopaedia entitled Pseudodoxia Epidemica. Browne alludes to Gaffarel's astrology in The Garden of Cyrus thus:
On the other hand, the Sorbonne rejected Gaffarel's work and ridiculed him; however, he gained the protection of the powerful Cardinal Richelieu, who made him his librarian and sent him off firsto to Italy, then to Greece and Asia to retrieve rare books (reportedly including manuscripts by Pico della Mirandola).