Background. US residents make 60 million international trips annually. Family practice providers need to be aware of travel-associated diseases affecting this growing mobile population. Objective. To describe demographics, travel characteristics and clinical diagnoses of US residents who present ill after international travel. Methods. Descriptive analysis of travel-associated morbidity and mortality among US travellers seeking care at 1 of the 22 US practices and clinics participating in the GeoSentinel Global Surveillance Network from January 2000 to December 2012. Results. Of the 9624 ill US travellers included in the analysis, 3656 (38%) were tourist travellers, 2379 (25%) missionary/volunteer/research/aid workers (MVRA), 1580 (16%) travellers visiting friends and relatives (VFRs), 1394 (15%) business travellers and 593 (6%) student travellers. Median (interquartile range) travel duration was 20 days (10-60 days). Pre-travel advice was sought by 45%. Hospitalization was required by 7%. Compared with other groups of travellers, ill MVRA travellers returned from longer trips (median duration 61 days), while VFR travellers disproportionately required higher rates of inpatient care (24%) and less frequently had received pre-travel medical advice (20%). Illnesses of the gastrointestinal tract were the most common (58%), followed by systemic febrile illnesses (18%) and dermatologic disorders (17%). Three deaths were reported. Diagnoses varied according to the purpose of travel and region of exposure. Conclusions. Returning ill US international travellers present with a broad spectrum of travelassociated diseases. Destination and reason for travel may help primary health care providers to generate an accurate differential diagnosis for the most common disorders and for those that may be life-threatening.