Gafni's focus is research on political, social and religious Jewish life during the Second Temple Period (516 BCE – 70 CE).

His book The Jews of Talmudic Babylonia: A Social and Cultural History was honored with the 1992 Holon Municipality Prize for Jewish studies.

In the book he seeks to "shed some light on what the Jews of the period (post destruction of the Second Temple), in Judea, as well as in diaspora, might have thought about their particular situation as a scattered people, and how these thoughts translated into concrete policies and subsequent measures that shaped and defined relationships among the various Jewish communities of Late Antiquity."

The most recent works published by Gafni are The Jewish Family – Metaphor and Memory, explaining the institution of Jewish marriage in Rabbinic times, and Irano-Judaica II which articulates the expressions and types of "local-patriotism" among the Jews of Sasanian Babylonia.

He has offered courses entitled "The Beginnings of Judaism", "The Great World Religions", and has lectured in institutions throughout Israel and North America.