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Return to South Africa, final years and death

Following growing pressure from the anti-apartheid movement both domestically and internationally, in 1990 State President Frederik Willem de Klerk reversed the ban on the African National Congress and other anti-apartheid organisations, and announced that Mandela would shortly be released from prison. Mandela was released in February 1990. He persuaded Makeba to try to return to South Africa; she obtained a six-day visa after months of effort, and entered South Africa using her French passport on 10 June 1990. Her arrival was a considerable event, featuring meetings, interviews, and singing by Brenda Fassie.

Makeba, Gillespie, Simone, and Masekela recorded and released her studio album, Eyes on Tomorrow, in 1991. It combined jazz, R&B, pop, and traditional African music, and was a hit across Africa. Makeba and Gillespie then toured the world together to promote it. In November she made a guest appearance on a US sitcom, The Cosby Show. In April 1992, she performed two concerts in Johannesburg, her first in South Africa since her exile in 1960. In the same year she starred in the film Sarafina! which centred on students involved in the 1976 Soweto uprising. Makeba portrayed the title character's mother, Angelina, a role which The New York Times described as having been performed with "immense dignity".

On 16 October 1999, Makeba was named a Goodwill Ambassador of the Food and Agriculture Organization of the United Nations. In January 2000, her album, Homeland, produced by the New York City based record label Putumayo World Music, was nominated for a Grammy Award in the Best World Music Album category. She worked closely with Graça Machel-Mandela, the South African first lady, advocating for children suffering from HIV/AIDS, child soldiers, and the physically handicapped. She established the Makeba Centre for Girls, a home for orphans, described in an obituary as her most personal project. She also took part in the 2002 documentary Amandla!: A Revolution in Four-Part Harmony, which examined the struggles of black South Africans against apartheid through the music of the period. Makeba's second autobiography, Makeba: The Miriam Makeba Story, was published in 2004. In 2005 she announced that she would retire and began a farewell tour, but despite having osteoarthritis, continued to perform until her death. During this period, her grandchildren Nelson Lumumba Lee and Zenzi Lee, and her great-grandchild Lindelani, occasionally joined her performances.

On 9 November 2008, Makeba fell ill during a concert in Castel Volturno, near Caserta, Italy. The concert had been organised to support the writer Roberto Saviano in his stand against the Camorra, a criminal organisation active in the Campania region. She suffered a heart attack after singing her hit song "Pata Pata", and was taken to the Pineta Grande clinic, where doctors were unable to revive her.