Background. Demographics, preferences on health care, and regional differences in pre-travel advice guidelines may influence the preparation of travelers to developing countries. Methods. A secondary data analysis of the database of a travelers' health survey conducted in Cusco in 2002 was performed. Data from those whose place of residence was North America or Western Europe were selected. Illness rates, vaccinations, prophylactic medication use, and general recommendations on disease prevention were compared between the two groups. Results. Data from 1,612 North Americans (NAM) and 3,590 Western Europeans (EUR) were analyzed. NAM were older, stayed longer in Cusco, and had less experience traveling to developing countries (p < 0.01). They reported being ill more often than EUR (58% vs 42%, p < 0.01). Diarrhea was more frequent among EUR (55.6% vs 46.7%, p < 0.01), and acute mountain sickness (AMS) was more frequent among NAM (52.8% vs 35.2%, p < 0.01). EUR sought advice from health care professionals (67.1% vs 52.0%, p < 0.01) and travel medicine practitioners (45.8% vs 37%, p < 0.01) more often. NAM used prophylactic medications more often (53% vs 48.6%, p = 0.00) and received a lower mean number of vaccines (1.97 ± 1.68 vs 2.63 ± 1.49; t-test 14.02, p < 0.01). Advice on safe sex and alcohol consumption was low in both groups, especially among NAM. Conclusions. Pre-travel preparation and travel-related illnesses varied between NAM and EUR. Improving consistency of pre-travel preparation based on the best evidence should become a priority among different national bodies providing travel medicine recommendations. © 2010 International Society of Travel Medicine.