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Abstract: In recent decades in South-Italy, drastic epidemiological changes in the pattern of the enterically transmitted diseases were recorded. This work aims to support the hypothesis that universal routine vaccination against hepatitis A started in Puglia in 1998 could be also effective in reducing contamination in seafood. Three studies on different samples of Mitylus edulis lamellibranch were conducted over 20years. Microbiological analysis measured both the standard bacteriological indexes (faecal coliforms, Escherichia coli, Salmonella spp.) and the presence of hepatitis A, enterovirus, norovirus and rotavirus. Between 1989 and 2009, the highest number of hepatitis A cases was reported in 1996 and in 1997 (mean incidence rate of 130 per 100,000). Since 1999, the number of cases progressively decreased, reaching 29 cases in 2006 (incidence rate of 0.7 per 100,000). A progressive improvement in vaccination coverage of newborns was recorded ranging from 1997 (38.3%) to 2005 birth-cohorts (63.4%). Vaccination coverage of 12-year-old adolescents was 67.6% (95% CI: 58.4–76.8%). Hepatitis A was detected in 3.7% of samples in the 1987 study, in 18.3% of samples in the 1999–2000 study and it was absent in the 2007 study. The decreasing of HAV circulation in humans and in shellfish provides support for the link between vaccination efforts and the safety of molluscs. [Copyright &y& Elsevier]