The objective of this study was to determine the risk factors for travelers' diarrhea (TD) reported by visitors to Cuzco, Peru. In this cross-sectional study, self-administered questionnaires looking at perceived occurrence of health problems and pre-travel health advice were obtained from departing travelers at Cuzco's International Airport between August and November 2002. A total of 5,988 travelers participated in the study. The mean age was 35 years, and 51% were women. The prevalence of TD was 24%. Factors associated with TD in the multivariable analysis were use of antibiotic prophylaxis (OR: 3.20), vaccination against cholera (OR: 1.44), history of advice for safe food and water consumption (OR: 1.46), being younger than 35 years of age (OR: 1.37), being a resident of the United States (OR: 1.28), not staying in hotels in Cuzco (OR: 1.13), and number of unsafe food or beverages consumed (OR: 1.04). Remaining in Cuzco < 1 week was a protective factor (OR: 0.58). TD is common among travelers to Cuzco. This study suggests that conventional recommendations are not invariably effective at decreasing TD. Copyright © 2006 by The American Society of Tropical Medicine and Hygiene.