Cardiovascular disease (CVD) is the leading cause of death among American Indians and Alaska Natives. Reducing CVD risk requires effective communication about risk factors and preventive behaviors. Messages should be designed with an understanding of where people seek health information, their perceptions of a hazard, and their perception of information sufficiency. We examined these components of message design to inform strategies to effectively communicate information about CVD to American Indians and Alaska Natives. We surveyed 220 adults who self-identified as American Indians or Alaska Natives at 2 Native-focused events in urban areas. Our survey included items on demographic characteristics, place of residence, sources of information used to learn about CVD, perceived information sufficiency, and perceptions about the importance of CVD as a health problem. Respondents used the internet (67%), their doctors (66%), friends and relatives (63%), brochures (62%), and television (61%) to learn about CVD. Participants aged 60 or older and those living on a reservation were more likely to use their doctor to learn about CVD than their younger (≤30 y) or urban peers. CVD was viewed as a major problem for American Indians and Alaska Natives (84%) and for Americans in general (86%). Most respondents felt moderately (54%) or well informed (37%) about CVD. Various information sources should be used to increase awareness about CVD. Special attention may be needed to optimize communication to American Indians and Alaska Natives aged 60 or older and people living on reservations. Further study is needed to determine how our findings can best inform effective interventions to reduce CVD morbidity and mortality among these populations.