Background: Estimates of travel-related illness have focused predominantly on populations from highly developed countries visiting low- or middle-income countries, yet travel to and within high-income countries is very frequent. Despite being a top international tourist destination, few sources describe the spectrum of infectious diseases acquired among travellers to the USA. Methods: We performed a descriptive analysis summarizing demographic and travel characteristics, and clinical diagnoses among non-US-resident international travellers seen during or after travel to the USA at a GeoSentinel clinic from 1 January 1997 through 31 December 2016. Results: There were 1222 ill non-US-resident travellers with 1393 diagnoses recorded during the 20-year analysis period. Median age was 40 (range 0-86 years); 52% were female. Patients visited from 63 countries and territories, most commonly Canada (31%), Germany (14%), France (9%) and Japan (7%). Travellers presented with a range of illnesses; skin and soft tissue infections of unspecified aetiology were the most frequently reported during travel (29 diagnoses, 14% of during-travel diagnoses); arthropod bite/sting was the most frequently reported after travel (173 diagnoses, 15% after-travel diagnoses). Lyme disease was the most frequently reported arthropod-borne disease after travel (42, 4%). Nonspecific respiratory, gastrointestinal and systemic infections were also among the most frequently reported diagnoses overall. Low-frequency illnesses (<2% of cases) made up over half of diagnoses during travel and 41% of diagnoses after travel, including 13 cases of coccidioidomycosis and mosquito-borne infections like West Nile, dengue and Zika virus diseases. Conclusions: International travellers to the USA acquired a diverse array of mostly cosmopolitan infectious diseases, including nonspecific respiratory, gastrointestinal, dermatologic and systemic infections comparable to what has been reported among travellers to low- and middle-income countries. Clinicians should consider the specific health risks when preparing visitors to the USA and when evaluating and treating those who become ill.