This study aimed to manage Helicobacter pylori (H. pylori) infection through a family-centered approach. It conducted a two-year follow-up on infected individuals' family members in Yichun, Jiangxi, China, to gain comprehensive insights into the transmission dynamics, treatment adherence, and associated risk factors of H. pylori within households. A retrospective analysis was performed on the data obtained from households in Yichun City that participated in the nationwide multicenter H. pylori prevalence study in 2021, along with the corresponding subsequent follow-up data. The collected information encompassed fundamental demographic details of the families, their lifestyle patterns, and the status of H. pylori infection. Among 514 households, 222 comprised two individuals, whereas 68 constituted larger families with five or more members. All member was infected in 9.34% of households. Larger family sizes (≥ 5 individuals) and higher generational counts were closely associated with H. pylori infection (e.g., family size >
6: OR 4.46, 95%CI 1.29 to 15.46). Adult age, marital status, and household members' infections were identified as primary risk factors (e.g., married individuals: OR 2.03, 95%CI 1.56 to 2.65). Students and previously uninfected individuals exhibited lower infection risks (e.g., tested as negative: OR 0.48, 95%CI 0.31 to 0.73). Maternal, paternal, or sibling infections were linked to increased risks of child infections (e.g., mother infected: OR 2.58 95%CI 1.37 to 4.87). Successful eradication in ≥ 2 individuals reduced the infection risk for other members (OR 0.25, 95%CI (0.07 to 0.89). H. pylori displayed noticeable clustering infection characteristics within families. This study lends support to family-based management strategies, but given suboptimal adherence to household management, there is a need to enhance education on the hazards of H. pylori before implementing screening programs.