Immigrants returning home to visit friends and relatives (VFR travelers) are at higher risk of travel-associated illness than other international travelers. We evaluated 3,707 VFR and 17,507 non-VFR travelers seen for pre-travel consultation in Global TravEpiNet during 2009-2011; all were traveling to resource-poor destinations. VFR travelers more commonly visited urban destinations than non-VFR travelers (42% versus 30%, P < 0.0001); 54% of VFR travelers were female, and 18% of VFR travelers were under 6 years old. VFR travelers sought health advice closer to their departure than non-VFR travelers (median days before departure was 17 versus 26, P < 0.0001). In multivariable analysis, being a VFR traveler was an independent predictor of declining a recommended vaccine. Missed opportunities for vaccination could be addressed by improving the timing of pre-travel health care and increasing the acceptance of vaccines. Making pre-travel health care available in primary care settings may be one step to this goal.