Background: Hepatitis B virus (HBV) infection, the predominant cause of hepatocellular carcinoma (HCC) worldwide, disproportionately affects Asian Americans. Limited data exist on the variability and characteristics of infection that determine disease progression risk within U.S. Asian ethnic subgroups., Methods: Retrospective analyses were conducted on a large, community-based HBV screening and treatment program in New York City (NYC). From 2004 to 2008, the program enrolled 7,272 Asian-born individuals. Determinants of HBV seroprevalence were calculated and risk factors for HCC progression were compared across Asian subgroups., Results: Among newly tested individuals, 13% were HBV positive. Seroprevalence varied significantly with age, gender, education, birthplace, and family history of infection. Chinese-born individuals, particularly from the Fujian province, had the highest seroprevalence (23.2% and 33.1%, respectively). Clinical and virologic characteristics placed HBV-infected individuals at significant risk for HCC. Significant differences in HCC risk existed among Asian subgroups in bivariate analysis, including age, gender, HBV viral load, and HBeAg status. Differences in HBV genotype and family history of HCC may further HCC risk among subgroups., Conclusions: Asian immigrants in NYC have a high prevalence of HBV infection and are at significant risk of disease progression and HCC. Although heterogeneity in HBV seroprevalence was found by Asian subgroups, HCC risk among infected individuals was primarily explained by age and gender differences. Country and province of birth, age, and gender may further explain seroprevalence differences., Impact: Findings provide estimates of HBV burden in Asian ethnic subgroups and identify high-risk groups to target for screening and treatment that can prevent HCC., (©2014 American Association for Cancer Research.)