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<b>Background</b>: Hepatitis B and C remain a major public health challenge in Greece, particularly amid demographic shifts, migration, and evolving socioeconomic conditions. Updated epidemiological data are essential to guide public health planning and prevention strategies. <b>Methods</b>: A repeated cross-sectional study was conducted among adults (n = 36,085) attending the General Hospital of Nikaia "Agios Panteleimon", Piraeus, Greece, from 2018 to 2024. Participants consisted of inpatients and outpatients, including recognized high-risk groups. Serological markers assessed current hepatitis B infection (HBsAg) and past or recent hepatitis C exposure (anti-HCV). Associations were examined using univariate and multivariate logistic regression, reporting adjusted odds ratios (aORs) and 95% confidence intervals (CIs). <b>Results</b>: Overall prevalence was 4.65% for HBsAg (n = 1677) and 6.6% for anti-HCV (n = 2378). Females had significantly lower odds compared to males for both markers (HBsAg aOR = 0.24, anti-HCV aOR = 0.77, both <i>p</i> < 0.001). Anti-HCV prevalence declined with age, with the ≥70 group showing the lowest odds (aOR = 0.24, <i>p</i> < 0.001). For HBsAg, older age groups also showed reduced odds, particularly ages 60-69 (aOR = 0.49, <i>p</i> < 0.001) and ≥70 (aOR = 0.75, <i>p</i> = 0.005). Compared to Attica region, most regions had significantly lower odds of both infections, including Thrace (HBsAg aOR = 0.08; anti-HCV aOR = 0.32, both <i>p</i> < 0.001), Crete (HBsAg aOR = 0.13; anti-HCV aOR = 0.35, both <i>p</i> < 0.001), and Macedonia (HBsAg aOR = 0.37; anti-HCV aOR = 0.64, both <i>p</i> < 0.001). Compared to 2018, the odds were markedly higher in 2023 and peaked in 2024 for both infections (anti-HCV aOR = 1.78; HBsAg aOR = 3.10, both <i>p</i> < 0.001 for 2024). High-risk social groups demonstrated substantially elevated odds of anti-HCV (aORs 3.9-5.51, all <i>p</i> < 0.001), but had lower odds of HBsAg (aORs 0.32-0.60, all <i>p</i> ≤ 0.001). <b>Conclusions</b>: Increasing prevalence trends, regional disparities, and pronounced differences among vulnerable groups highlight the urgent need for strengthened screening, vaccination, and targeted hepatitis B and C prevention strategies, particularly among healthcare-attending and high-risk populations in Greece.