When R. Isserles published his Torat Hattat on issur ve-hetter (on the dietary laws), R. Hayyim published a vigorous polemic against it in his Vikku'ah Mayim Hayyim. The introduction to the work was couched in such strong language both against R. Isserles and R. Joseph Caro that it was omitted from editions after the first (Amsterdam, 1712).

R. Hayyim wrote a number of other works. His Sefer ha-Hayyim, which he wrote in two months while he was confined to his house on account of a plague in 1578, is a moral and ethical dissertation. In style and language it is reminiscent of the pietistic works, and in fact his brother refers to him as "he-Hasid." His Ez Hayyim on Hebrew grammar (written in 1579) is still in manuscript. He was inspired to write it because of the criticism of Christian Hebrew scholars who accused the Jews not only of neglecting the study of Hebrew in favor of the Talmud, but even of forbidding it. He admits that he used the grammatical works of these detractors as one of his sources. He attributes the neglect of the study of Hebrew grammar to the fact that in the "bitter and long exile... it was impossible to encompass all subjects in the curriculum, for which reason alone the early authorities, especially the Hasidei Ashkenaz, confined their instruction to the Talmud" (Introduction). He also wrote Be'er Mayim Hayyim, a supercommentary on Rashi's Pentateuch commentary, and Iggeret ha-Tiyyul (Prague, 1605) consisting of explanations of talmudic passages using the methods of Pardes, in alphabetical order.