Twelver Shi'ism (Arabic: اِثْنَا عَشَرِيَّة, romanized: Ithnā ʿAshariyya) is the largest branch of Shia Islam, comprising about 85% of all Shia Muslims. The term Twelver refers to its adherents' belief in twelve divinely ordained leaders, known as the Twelve Imams, and their belief that the last Imam, Imam al-Mahdi, lives in occultation (ghayba) and will reappear as "the awaited Mahdi" (al-Mahdi al-muntazar) alongside the awaited Nabi Isa, Jesus, The Messiah (Al-Masih) son of Bibi Mariam (The Virgin Mary), in order to restore justice and peace.

Twelver Shi'as believe that the Twelve Imams are divinely appointed as both spiritual and political successors to the Islamic prophet Muhammad, and that they possess special knowledge and authority to guide the Muslim community. According to Twelver theology, the Twelve Imams are exemplary human individuals who rule over the Muslim community (Ummah) with justice, and are able to preserve and interpret the Islamic law (Sharia) and the esoteric meaning of the Qur'an. The words and deeds (sunnah) of Muhammad and the Imams are a guide and model for the Muslim community to follow. As a result, Muhammad and the Imams must be free from error and sin, a doctrine known as Ismah (literally 'protection') or infallibility, and must be chosen by divine decree, or nass, through Muhammad.

Globally, there are about 170–255 million Twelvers: most of the inhabitants of Iran, Iraq, and Azerbaijan, about half of the Muslim population of Bahrain, and sizeable minorities in Lebanon, India, Pakistan, Afghanistan, Saudi Arabia, Bangladesh, Kuwait, Oman, the UAE, and Qatar. Iran is the only country where Twelver Shi'ism is the state religion.

Twelvers share many tenets with other Shi'ite sects, such as the belief in the Imamate. The Isma'ili and Nizari branches believe in a different number of Imams and, for the most part, a different path of succession regarding the Imamate. They also differ in the role and overall definition of an Imam. Twelvers are also distinguished from Isma'ilis by their belief in Muhammad's status as the "Seal of the Prophets" (Khatam an-Nabiyyin), in rejecting the possibility of abrogation of Sharia laws, and in considering both esoteric and exoteric aspects of the Qur'an. Alevis in Turkey and Albania, and Alawites in Syria and Lebanon, share belief in the Twelve Imams with Twelvers, but their theological doctrines are markedly different.

The term Twelver is based on the belief that twelve male descendants from the family of Muhammad, starting with Ali ibn Abi Talib and ending with Muhammad al-Mahdi, are Imams who have religious and political authority.

The Twelvers are also known by other names:

In 610, when Muhammad received the first revelation, Ali was 10 years old. At the time of Muhammad, some of the supporters of Ali, particularly Miqdad ibn al-Aswad, Salman the Persian, Abu Dharr al-Ghifari, and Ammar ibn Yasir were called the Shiites of Ali. The division of Islam into Shia and Sunni traces back to the crisis of the succession to Muhammad. The followers of Ali fought with some of the Quraysh and some of the companions of Muhammad like Talhah and Zubayr. As most of his supporters were in Iraq, Ali moved the capital of Islam to Kufa and there began to fight against Mu'awiyah, who rejected giving allegiance to Ali. The death of Husayn played an important role in the spread of Shi'ism in the regions of Iraq, Yemen and Persia. At the end of the first century, the influential leaders in the government established the city of Qom for the settlement of the Shia.

Muhammad Al-Baqir was teacher of law for 20 years and a reporter of hadith. He also introduced the principle of Taqiyya. Al-Baqir narrated many a hadith about Jurisprudence and other religious sciences which based the foundations for the Shia instructions. With change in political situations and a suitable conditions for the development of religious activities and the time of elaborating the religious sciences, Ja'far al-Sadiq had an important role in forming the Shia Jurisprudence.