The grand vizier () was one of the highest ranking offices in Safavid Iran. From at least the tenure of Mirza Shah Hossein, they held the honorific title of E'temad ol-Dowleh.

During the 16th century, the authority of the grand vizier was a reflection of the shah’s own authority. Grand viziers held less prominence during the early Safavid era, as shahs like Shah Tahmasp I () and Shah Abbas I () were more engaged in the administration. The Turkmen Qizilbash leaders also held a level of influence that limited the authority of the grand vizier during the majority of the 16th century.

From the 16th late century onward, other prominent members of the court limited the power of the grand vizier, such as the steward of the royal court (nazer-e boyutat), the secretary-general of the royal secretariat (nazer-e daftar-e homayun), the treasurer-general (mostowfi ol-mamalek), the military commanders, or by one or more of the shah's favorites, as well as members of the harem. Nevertheless, the shah's patronage could elevate the grand vizier above all opposition, ensuring his command over the court uncontested.

The power of the grand vizier increased substantially in the 17th century as a result of the diminished authority of the Qizilbash leaders and the more fragmented and scattered makeup of the ruling class (Tajiks, eunuchs, royal women, gholams, and Qizilbash). From 1669 onwards, the grand vizier was usually from a tribal (Kurdish or Turkmen) background. With their entry to the office, the Qizilbash thus regained some of their lost authority. This entry to a Tajik-only office was due to the grand vizier's rise to prominence as the undisputed head of the central bureaucracy. The Qizilbash had by now accepted to share authority with the gholams and had been integrated into the Safavid bureaucracy. It also demonstrated how the Turkmens successfully assimilated into Persian administrative culture. Aside from their various talents, grand viziers were primarily selected for their administrative skills.

The grand vizier was the head of the royal council, the highest governing authority in the government.

List of grand viziers Name(s) Date Family/Tribe Monarch Amir Zakariya 1501–1507 Kujuji family Ismail I Mahmud Jan Daylami 1502/3–1507 Daylami family Ismail I Najm-e Sani 1508–1510 Khuzani family Ismail I Aqa Kamal al-Din Hossein Monshi Qomi 1509–1514 Ismail I Mirza Shah Hossein 1514–1523 Ismail I Jalal al-Din Mohammad Tabrizi 1523–1524 Kujuji family Ismail I, Tahmasp I Qadi Jahan Qazvini 1524 Tahmasp I Mirza Jafar Savaji 1525–1531 Savaji family Tahmasp I Ahmad Beg Nur Kamal 1531–1533/34 Nur Kamaliya family Tahmasp I Khvajeh Sa'd al-Din Enayat Khuzani & Khvajeh Mo'en Yazdi 1534–1535 Khuzani family (Sa'd al-Din Enayat only) Tahmasp I Khvajeh Sa'd al-Din Enayat Khuzani & Qadi Jahan Qazvini 1535 Khuzani family (Sa'd al-Din Enayat only) Tahmasp I Qadi Jahan Qazvini 1535–1551 Tahmasp I Khvajeh Amir Beg Mohrdar, Khvajeh Ghayath al-Din Ali & Aqa Mohammad Farahani Kajaji 1551 Kujuji family (Khvajeh Amir Beg only) Tahmasp I Mirza Beg Sabaqi Abhari & Khvajeh Seif al-Moluk Tehrani 1552–1553 Tahmasp I Masum Beg Safavi 1553–1568 Sheykhavand family Tahmasp I Emir Sayyed Sharif-e Sani 1568–1569 Tahmasp I Mir Sayyed Hossein Farahani & Khvajeh Kamal al-Din Ali 1573–1574 Tahmasp I Mirza Shokrollah Isfahani 1576 Ismail II Mirza Salman Jaberi 1577–1583 Jaberi Ansari family Ismail II, Mohammad Khodabanda Mirza Hedayatollah 1583–1586 Khuzani family Mohammad Khodabanda Mirza Mohammad Monshi 1586 Kujuji family (maternal side) Mohammad Khodabanda Mirza Shah Vali 1587 Khuzani family Abbas I Mirza Lotfi 1587 Abbas I Mirza Mohammad Monshi 1588 Kujuji family (maternal side) Abbas I Mirza Lotfollah Shirazi 1589–1591 Abbas I Hatem Beg Ordubadi 1591–1610 Ordubadi family Abbas I Mirza Taleb Khan Ordubadi 1610–1621 Ordubadi family Abbas I Salman Khan Ustajlu 1621–1624 Ustajlu tribe Abbas I Khalifeh Soltan 1624–1632 Khalifeh family Abbas I, Safi Mirza Taleb Khan Ordubadi 1632–1634 Ordubadi family Safi Saru Taqi 1634–1645 Safi, Abbas II Khalifeh Soltan 1645–1654 Khalifeh family Abbas II Mohammad Beg 1654–1660 Abbas II Mirza Mohammad Karaki 1661–1669 Karaki family Abbas II, Suleiman I Shaykh Ali Khan Zanganeh 1669 – March 1673 Zangana tribe Suleiman I Vacant March 1673 – June 1674 Suleiman I Shaykh Ali Khan Zanganeh June 1674 – 1689 Zangana tribe Suleiman I Mohammad Taher Vahid Qazvini 1691 – May 1699 Suleiman I, Soltan Hoseyn Mohammad Mo'men Khan Shamlu May 1699 – 1707 Shamlu tribe Soltan Hoseyn Shahqoli Khan Zanganeh 1707–1715 Zangana tribe Soltan Hoseyn Fath-Ali Khan Daghestani 1715–1720 Shamkhal family of Kumukh Soltan Hoseyn Mohammad Qoli Khan Shamlu 1720–1721 Shamlu tribe Soltan Hoseyn Rajab Ali Beg ? Soltan Hoseyn Mohammad Ali Khan Mokri 1722 Soltan Hoseyn, Tahmasp II Mortezaqoli Khan 1723 Tahmasp II Mirza Abdol-Karim 1724 Tahmasp II Farajollah Khan Abdollu ? Tahmasp II Mirza Mohammad Hossein ? Tahmasp II Mirza Abdollah 1724 Tahmasp II Mirza Mo'men Qazvini 1725 Tahmasp II Mirza Mohammad Rahim 1728–1730 Tahmasp II Rajab Ali Khan 1731 Tahmasp II

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