Background: Although cardiovascular disease (CVD) is the leading cause of mortality in Latin American women, limited data exist on CVD perceptions in this population. This study aimed to assess CVD awareness and knowledge of women from Santiago, Chile. Methods: This was a cross-sectional study conducted in women 35 to 70 years old. A multistage probability sampling (stratified by age and socioeconomic level) was used for participant selection. Participants completed a home survey about knowledge of CVD, risk factors, and perceived risk (based on standardized questions from the American Heart Association awareness survey). Results: 723 women participated in the study (mean age: 51 ± 9 years; 17.6% with high education level). Only 9.3% of the respondents mentioned CVD as women's primary health problem, whereas 22.7% and 16.1%, respectively, listed breast cancer and other cancers. When asked to identify the leading cause of women's death, only 14.4% identified CVD compared to 69.1% who recorded cancer. Older women (≥ 55 years) more likely identified CVD as the main cause of death: (OR 2.9: 95% CI = 1.8-4.5) versus younger women (<55 years). CVD family history was also associated with higher awareness of CVD as the leading cause of death (OR 1.7: 95% IC; p = 1.1-2.6). Instead, women with middle education level were less likely to mention CVD as the main women's killer. Conclusions: Chilean women from Santiago have a low awareness of CVD as the leading cause of death and do not recognize CVD as their prominent health problem. Efforts should focus on increasing awareness and knowledge about CVD especially in young women.