Recent reports have linked air travel with venous thrombo-embolism (VTE). Risk factors and associated features of this link are poorly understood. We have accumulated clinical data from a relatively large cohort of patients with traveler's thrombosis. A total of 86 patients who developed venous thromboembolism within 28 d of flying were questioned concerning traveling habits, medical history (including risk factors for VTE) and characteristics of the index flight. Of the patients, 72% had at least one risk factor for VTE (excluding thrombophilia) prior to their flight. Of interest, 87% of VTE cases occurred following either a return trip or after an outward journey involving long trips made up of sequential flights. In only two cases could no identifiable risk factor or earlier journey be found. Duration of flights ranged from 2 to 30 h. Of responders, 38% presented with chest symptoms; 92% with VTE developed symptoms within 96 h of their flight. We conclude that the majority of VTE associated with air travel occur in those with identifiable risk factors prior to their flight, and that sequential flights may increase this risk.