Epidemiologic and clinical data suggest that Helicobacter pylori infection is a contributing factor in the progression of atherosclerosis. However, the specific cardiovascular disease risk factors associated with H. pylori remain unclear. We performed a cross-sectional study of 37,263 consecutive healthy subjects who underwent a routine health check-up. In multivariable log Poisson regression models adjusted for potential confounders, the associations of H. pylori seropositivity with higher LDL-C (relative risk [RR], 1.21; 95% confidence interval [CI], 1.12-1.30) and lower HDL-C level (RR, 1.10; 95% CI, 1.01-1.18) were significant and independent. In multiple linear regression analyses, H. pylori infection was significantly associated with higher total cholesterol level (coefficient = 2.114, P < 0.001), higher LDL-C level (coefficient = 3.339, P < 0.001), lower HDL-C level (coefficient = -1.237, P < 0.001), and higher diastolic blood pressure (coefficient = 0.539, P = 0.001). In contrast, H. pylori infection was not associated with obesity-related parameters (body mass index, waist circumference), glucose tolerance (fasting glucose, glycated hemoglobin), and systolic blood pressure. We found that H. pylori infection was significantly and independently associated with dyslipidemia, but not with other cardiometabolic risk factors, after adjusting for potential risk factors of atherosclerosis.