MF59-adjuvanted seasonal trivalent inactivated (ATIV) vaccine licensed since 1997 and MF59-adjuvanted pandemic H1N1 vaccines have been distributed to approximately 80M persons. Addition of the emulsion adjuvant to inactivated vaccine formulations provides for higher levels of antibody to the viral hemagglutinin (HA) in less responsive older adults, infants and children which, in the case of the pandemic vaccine, allowed only 3.75 µg of the HA to be immunogenic. The adjuvant also stimulates production of more broadly-reactive antibodies against strains that are mismatched to those in the vaccine, a potential advantage in the face of perennial influenza virus antigenic drift. In a field trial, ATIV was 89% efficacious in preventing laboratory-confirmed influenza in 6-65 years old by 23% compared to unadjuvanted vaccine, in an observational study. The effectiveness of MF59 adjuvanted split pandemic H1N1 vaccine was 74% overall. Unadjuvanted pandemic vaccine was poorly immunogenic in HIV-infected persons, whereas their responses to MF59-adjuvanted vaccine were similar to those of healthy controls. Analyses of the clinical trials and pharmacovigilance databases and observational studies have shown that while MF59-adjuvanted influenza vaccines are more locally reactogenic, they have not been associated with an increased risk for various adverse effects (AE) of special interest, including unsolicited neurological or autoimmune events.