This epistle, with a commentary by Joseph ibn Shem-Tov and an introduction by Isaac Akrish, was first printed at Constantinople in 1554, and was republished in A. Geiger's Melo Chofnajim, 1840, in the collection Ḳobeẓ Wikkuḥim, 1844, and in P. Heilpern's Eben Boḥan, part 2, 1846.

According to an account written at the top of one of the manuscripts of the epistle, Duran and his friend David Bonet Bonjourno made up a plan to emigrate to Palestine in order to return to Judaism.

The two friends set out on their journey, getting as far as Avignon, where they met up with another converso, Paul of Burgos (who had become a believing Christian priest, and had achieved the rank of Bishop).

The notarial ledgers of Perpignan show several transactions in 1393 and 1394 in which Duran (known officially by his Christian name Honoratus de Bonafe) moved assets across the border to France.

Connected with this epistle is the polemic Kelimmat ha-Goyim ("Shame of the Gentiles"), a criticism of Christian dogmas, written in 1397 at the request of Don Hasdai Crescas, to whom it was dedicated.

Using the knowledge of Latin he gained from his medical studies and the indoctrination he received as a converso, he identifies what he sees as internal contradictions within the New Testament, and discrepancies between its literal text and church dogma.

In 1395 Duran compiled an almanac in twenty-nine sections entitled Ḥesheb ha-Efod ("The ephod's girdle"), and dedicated to Moses Zarzal, writer and physician to Henry III of Castile (1379–1406).

That Duran was familiar with the philosophy of Aristotle as interpreted by Muslim philosophers, is apparent from his synoptic commentary on Maimonides' The Guide for the Perplexed, which was published at Sabbionetta in 1553, at Jeßnitz in 1742, and at Zhovkva in 1860.

Duran's chief work, praised by both Christians and Jews, is his philosophical and critical Hebrew grammar, Ma'aseh Efod ("The making of the ephod"), containing an introduction and thirty-three chapters, and finished in 1403.

In 1393 Duran wrote a dirge on Abraham ben Isaac ha-Levi of Gerona, probably a relative; three letters containing responsa, to his pupil Meïr Crescas; and two exegetical treatises on several chapters of II Samuel, all of which have been edited as an appendix to the Ma'aseh Efod.