Abstract Background Travellers' diarrhoea (TD) is the most common infectious disease among travellers. In the Netherlands, stand-by or prophylactic antibiotics are not routinely prescribed to travellers. This study prospectively assessed the incidence rate, risk factors, and treatment of TD among immunocompetent travellers. Methods Persons who attended the travel clinic of the Public Health Service Amsterdam in 2006-2007 before short-term travel to tropical and subtropical countries were invited to answer a questionnaire regarding sociodemographics and travel purpose; they were also asked to keep a daily structured travel diary, recording their itinerary, symptoms, and self-medication or consultation with a doctor. Diarrhoea episodes containing blood or mucous were considered severe. Results Of 1202 travellers, the median age was 38 years, and the median travel duration 3 weeks. Of all episodes, 96% were mild. The median duration of TD was 2 days and significantly shorter in subsequent episodes compared to first episodes (p < 0.0005). Of first episodes 38% started in the first travel week. The incidence rate (IR) for first episodes was 2.49 (95% confidence interval [CI], 2.30-2.70) per 100 travel days, with the highest IR among travellers to South-Central and West Asia. The IR for first and subsequent episodes was comparable. Risk factors for first episodes included female sex, a Western country of birth, and tourism as the purpose of travel. The lowest risk was in travellers to South America. An independent risk factor for subsequent episodes was female sex. In total, 5% of travellers used antibiotics; of those, 92% had mild diarrhoea, and 53% received antibiotics over the counter. Conclusions TD is common among travellers, but the overall course is mild, not requiring treatment. The incidence rates for first and second episodes are comparable. Female sex is a risk factor for the first episode, as well as subsequent ones. Prescription antibiotics are not needed in short-term healthy travellers.