R. Bertinoro's fame rests on his commentary on the Mishnah which was completed in Jerusalem and published in Venice (1548–49). It has become the standard commentary on the Mishnah as is Rashi's on the Talmud. This commentary was published with the text in almost every edition of the Mishnah. Written in an easy, lucid style, it draws largely on Rashi, often quoting him literally, and on Maimonides, whose rulings he cites. For the sections of Mishnah which have no Talmud he drew on the commentary of R. Samson b. Abraham of Sens and of R. Asher b. Jehiel. Tosefot Yom Tov, by R. Yom Tov Lipmann Heller was so named because its purpose was to serve as an addition (tosefet) and exposition, supplement and work of source reference to the Mishnah commentary of Obadiah of Bertinoro. In it are traced the sources of the Bertinoro commentary, explained obscurities, examined and also criticized its conclusions in the sphere of halakhah, and made linguistic comments. In it R. Heller explained the words grammatically, noted the halakhah on the basis of the Talmud and the rishonim and aharonim and took care to establish accurate readings, most of which he added to the second edition of his commentary, through clarification and elucidation of the text on the basis of various manuscripts and earlier published works. Heller endeavored to reconcile the contradictions between one Mishnah and another by means of straightforward and logical rationalization. All his comments are formulated with the utmost simplicity—and here he follows in the footsteps of his teacher R. Judah Loew b. Bezalel, who opposed the method of pilpul. Despite his positive attitude to Kabbalah, he refrained from relying upon it in deciding the halakhah, since "in explaining the Talmud, we have no dealings at all with esoteric matters" (Ma'adanei Yom Tov; Ber. 1). In his opinion the Mishnah might be interpreted differently from the explanation given in the Talmud, "providing no decisions which contradict the view of the authors of the Gemara are given" (Tosefot Yom Tov to Naz. 5:5). In his introduction he formulated his attitude to the commentary of Bertinoro: "My task, however, is to examine carefully in the Mishnah in order to see whether anything requires explanation that has not been explained in the commentary of the Rav [Bertinoro], or whether there is a contradiction from some other Mishnah to which he has not drawn attention, and also whether there is anything in his commentary for which an explanation and reason has to be given, as well as if there be any contradiction in the commentary itself, and more so from the Mishnah.

שער-מעטפת. נוסח השער מהוצאת אמשטרדם תקי"א-תקי"ב, וכן ההסכמות. גוף הספר על-פי קראקא תרמ"ג, בהשמטת "לוח הטעות" שבחלקו תוקן בפנים. הסכמות חדשות: ר' ישראל בן מוהר"ב [ברוך האגר מוויזניץ], ג חקת תרע"א; ר' יצחק אייזיק [ווייס], סאפינקא, ט אייר תרמ"א [צ"ל: תרע"א]; ר' יודא ג"וו [גרינוואלד], סאטמאר, י תמוז תרע"א; ר' אברהם יוסף ג"וו, חוסט, א תמוז תרע"א; ר' יהודא יואל [דייטש], גאניטש, כא למב"י [ו אייר] תרע"א.