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Seafood can vehiculate foodborne illnesses from water to humans. Climate changes, increasing water contamination and coastlines anthropization, favor the global spread of <i>Vibrio</i> spp. and the occurrence of antibiotic-resistant isolates. The aim of this study was to evaluate the spread of potentially pathogenic <i>Vibrio</i> spp. in fishery products collected in Sicily and to assess their antibiotic resistance. Bacteriological and molecular methods were applied to 603 seafood samples to detect <i>V. parahaemolyticus</i>, <i>V. cholerae</i>, <i>V. vulnificus</i>, and <i>Vibrio alginolyticus</i> in order to assess their pathogenicity and antimicrobial resistance. About 30% of bivalves and 20% of other fishery products were contaminated by <i>Vibrio</i> spp.; <i>V. parahaemolyticus</i> accounted for 43/165 isolates, 3 of which were carrying either <i>tdh</i> or <i>trh</i>; <i>V. cholerae</i> accounted for 12/165 isolates, all of them non-O1 non-O139 and none carrying virulence genes; and <i>V. vulnificus</i> accounted for 5/165 isolates. The highest rates of resistance were observed for ampicillin, but we also detected strains resistant to antibiotics currently included among the most efficient against <i>Vibrio</i> spp. In spite of their current low incidence, their rise might pose further issues in treating infections; hence, these results stress the need for a continuous monitoring of antimicrobial resistance among fishery products and an effective risk assessment.