Background and aims: The role of Helicobacter pylori (H. pylori) infection in carotid atherosclerosis remains inconsistent and sometimes controversial. We aimed to determine whether H. pylori infection is associated with carotid atherosclerotic plaques in a large number of Chinese adults. Methods: We recruited 108,210 Chinese adults who participated in a standard medical screening with both carotid ultrasonic examination and C-13-urea breath test for H.pylori infection from two Chinese cohorts. A total of 93,915 adults were included in the analysis after excluding participants with cardiovascular disease (CVD) and carotid plaques at baseline. Hazard ratio (HR) for developing carotid plaques by H. pylori infection was analyzed using the Cox proportional hazard model, with socio-demographic and clinical factors adjusted. Findings across cohorts were pooled by meta-analyses. Results: 11,208 (13.13%) participants occurred carotid plaques at a median follow-up of 20 months in the MN cohort, while 1279 (14.95%) participants occurred carotid plaques at a median follow-up of 24 months in the MJ cohort. Compare with participants without H. pylori infection, participants with H. pylori infection were more likely to occur carotid plaques. After adjusting for age, sex, annual personal income, body mass index, blood pressure, blood glucose, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and estimated glomerular filtration rate, the HR was 1.04 (95%CI: 1.01-1.08). After further adjusting for education level, marital status, smoking status, alcohol drinking status, physical activity, and family history of CVD, the HR changed minimally. Additional sensitivity analyses confirmed the robustness of the results. Significant interactions of age, sex, blood pressure, blood glucose, or chronic inflammation were not observed in this research. Conclusions: H. pylori infection was associated with carotid plaque onset in a large number of Chinese adults without previous CVD. These data suggested that the prevention of H. pylori infection may reduce the burden of carotid atherosclerosis. (C) 2021 The Authors. Published by Elsevier B.V.