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The objective was to determine the etiology of diarrhea among expatriate residents living in a developing country and identify risk factors for travelers' diarrhea that are difficult to evaluate in tourist populations. Among expatriate residents treated at a travel medicine clinic in Katthmandu, Nepal, the dominant risk factors for diarrhea included younger age (P.003), shorter duration of stay in Nepal (P <.0001), and eating out in restaurants (P.013). Raw vegetables, salads, fresh fruit, or ice served in restaurants were not statistically associated with diarrhea. Longer duration of residence was linearly correlated with protection. Enteric pathogens were identified in 44 (64%) of 69 residents with diarrhea compared with 100 (83%) of 120 tourists with diarrhea, with enterotoxigenic E. coli, Campylobacter, and Shigella predominant for both groups. Pathogens were also found in stools from 32 (37%) of 87 asymptomatic resident controls and 13 (52%) of 25 tourist controls. The attack rate of diarrhea among expatriates was estimated to be 49% (95% confidence interval, 37-61%) per month during the first two years of residence. The highest risk months were April-July. In conclusion, diarrhea among expatriates in a highly endemic environment is a persistent risk. The extremely high prevalence of enteric pathogens an%ng asymptomatic persons reflects widespread exposure. The most important risk factors for travelers' diarrhea are difficult to modify, including younger age, duration of stay, eating in restaurants, and seasonality. Preventive dietary recommendations may not be fully protective, suggesting that pre-travel advice should emphasize empiric treatment in addition to strategies to avoid exposure.