We aimed to assess the association between metabolic syndrome (MS) and hepatitis B/C virus infection using a large population-based study. A population-based cross-sectional study design was adopted with a total of 53,528 subjects being enrolled from the integrated multiple diseases screening program in Keelung, Taiwan. Evidence of past hepatitis B/C infection, acquired during childhood or as a young adult, was identified during the two-stage liver cancer screening part of the process. Information on biochemical markers and anthropometric measures related to MS, such as fasting blood sugar, triglyceride and high-density lipoprotein (HDL), abdominal circumference and blood pressure (BP), were collected routinely while screening for hypertension, type 2 diabetes, and hyperlipidemia. Logistic regression was used to estimate odds ratios and related 95% confidence intervals for the associations between MS and hepatitis B/C infection. High blood pressure (SBP > or = 135 mmHg or DBP > or = 85 mmHg) (adjusted odd ratio: 0.89 (0.83-0.94)) and high triglyceride (> or = 150 mg/dl) (adjusted odds ratio: 0.65 (0.60-0.69)) were, after adjusting for gender and age, inversely associated with being HBsAg positive (P<0.05). The likelihood of developing MS was lower in the HBsAg positive than the HBsAg negative (adjusted odds ratio: 0.84 (0.76-0.93)). A positive association between being anti-HCV positive and having low serum HDL (male <40 mg/dl, female <50 mg/dl) was also noted (adjusted odds ratio: 1.61 (1.37-1.88) after controlling for gender and age). High triglyceride was inversely associated with being anti-HCV positive (adjusted odds ratio: 0.63 (0.55-0.71). There is an inverse association between MS and hepatitis B virus infection whereas the association was heterogeneous for HCV infection with a positive association with abnormal serum HDL but an inverse association with hypertriglyceridemia.