Purpose: The objective of this study was to investigate the prevalence and molecular characteristics of Vibrio parahaemolyticus isolates from fecal samples of patients in Nantong, China. Methods: From 2018 to 2021, a total of 106 clinical cases and samples of V. parahaemolyticus infection were collected. The virulence genes, serotypes and antibiotic resistance of these isolates were analyzed. Additionally, pulsed-field gel electrophoresis (PFGE) was used to analyze the homogeneity of the isolates. Results: Outbreaks of V. parahaemolyticus infection were concentrated in the summer, with seafood consumption being the primary contributing factor, followed by meat and meat products. tlh+tdh+trh-was confirmed as the most frequently detected virulence genotype among the clinical isolates. 16 serotypes were identified, and O3:K6 was the dominant serotype in Nantong. The antimicrobial susceptibility testing revealed the highest resistance rate to cefazolin (99.1%, 104/106), followed by ampicillin (64.2%, 68/106) and tetracycline (29.2%, 31/106). Fourteen resistant phenotypes were identified, with ampicillin-cefazolin being the most prevalent. The multiple antibiotic resistance (MAR) index ranged from 0.07 to 0.36. PFGE typing clustered isolates with similarity greater than 85% into ten genetic clusters (A-J). Conclusion: Clinical isolates generally exhibited pathogenicity and drug resistance, with some isolates displaying high homology. Clusters C, E, and G were the predominant circulating clusters in this area, posing a potential risk of recurrent outbreaks, which demanded our vigilance.