Little is known about the characteristics of acute viral hepatitis cases in the United States (US)–Mexico border region. We analyzed characteristics of acute viral hepatitis cases collected from the Border Infectious Disease Surveillance Project from January 2000–December 2009. Over the study period, 1,437 acute hepatitis A, 311 acute hepatitis B, and 362 acute hepatitis C cases were reported from 5 Mexico and 2 US sites. Mexican hepatitis A cases most frequently reported close personal contact with a known case, whereas, US cases most often reported cross-border travel. Injection drug use was common among Mexican and US acute hepatitis B and C cases. Cross-border travel during the incubation period was common among acute viral hepatitis cases in both countries. Assiduous adherence to vaccination and prevention guidelines in the US is needed and strategic implementation of hepatitis vaccination and prevention programs south of the border should be considered.