Hepatitis E virus (HEV) is a common cause of acute viral hepatitis. Virus genotypes 1 and 2 infect humans in developing countries by the fecal–oral route. To assess attack rates and disease incidence for travelers, we prospectively studied 604 long-term travelers to subtropical and tropical countries. Participants donated blood samples pretravel and posttravel and kept a diary. A total of 89/604 (15%) pretravel samples were positive for HEV IgG by ELISA, suggesting previous HEV infection. Seroconversion for HEV was found for 19/515 travelers (attack rate 3.7%, incidence 1.8 cases/1,000 person-weeks). We believe there is a substantial risk for acquiring HEV infection among long-term travelers. Although HEV infection does not seem to be a major problem in this healthy cohort, hygienic measures should be stressed in all pretravel health advice, particularly for pregnant women and immunocompromised travelers who are at risk for severe disease.