Transportation is a social determinant of health, and rural and urban locations are demonstratively different in their transportation availability and infrastructure. Rural and urban locations in the United States also differ in their socio-demographic and health profiles, with rural populations tending to be older, sicker, and poorer than their urban counterparts. Little is known, however, about how perceptions of transportation in the U.S. and adaptations to travel-limiting health conditions differ by geographic location. Using data from the 2009 National Household Travel Survey (n = 204,035), we found differences by geographic location in transportation concerns. For example, rural residents were more likely to list price of travel as their biggest concern and less likely to list highway congestion, availability of public transportation, and issues with other drivers as their biggest concern, compared with urban residents. Among respondents with health conditions that limit travel (n = 17,332), we found differences by location in adaptations to such conditions, with rural residents being less likely to reduce their travel, even if it may be safer to do so. Urban residents with travel-limiting health conditions were more likely than their rural counterparts to limit travel to daytime hours and to use reduced fare taxis and other specialized transportation services, which are not as readily available in rural locations. These findings call for attention to cost and availability of alternative transportation options for individuals with health conditions that make driving difficult, especially in rural areas.