OBJECTIVE Metabolic syndrome (MS) is prevalent and is associated with adverse outcomes of liver disease.We evaluated the prevalence of MS and its influence on alanine aminotransferase (ALT) levels and fibrosis, as estimated by the aspartate aminotransferase- to-platelet ratio index (APRI), in a large, multiethnic North American cohort with chronic hepatitis B (HBV) infection. RESEARCH DESIGN AND METHODS Adultswith chronicHBVfrom21centerswithintheU.S.andCanadawereevaluatedat baseline and for up to 5 years (median 3.7 years) of follow-up. MSwas defined as the presenceofatleast threeoffivecriteriaincludingwaist circumference,bloodpressure, glucose, triglyceride, and HDL levels. RESULTS Analysis included 777 participants, ofwhom171 (22%) hadMS. Participants with MS (vs. those without MS) were older (median age 54.4 vs. 40.2 years), more oftenmale (61%vs. 51%), and born in the U.S./Canada or had immigrated >20 years ago (60% vs. 43%).MSwasnotassociatedwithALTorAPRIatbaseline.Uponadjustedmultivariable analysis of serial ALT values, ALTwas significantly higher (mean 12%; P = 0.02) among those withMS at baseline and even higher (mean 19%; P = 0.003) among those with persistent MS compared with those with persistent absence of MS. MS was not associated with serial APRI on follow-up. CONCLUSIONS MS was prevalent in this HBV cohort and was independently associated with higher ALT levels longitudinally. These findings highlight the importance of screening forMS and the potential for MSto influence ALT and its interpretation in the context of HBV treatment decisions.