Background: Previous research suggests that the presentation of acute coronary syndromes (ACS) may differ in women and men. No study has prospectively evaluated the role of a comprehensive set of typical and atypical symptoms and whether different symptoms on presentation predict ACS diagnosis in women and men. Methods and Results: We directly observed 246 women and 276 men seen in the emergency department with symptoms suggestive of ACS and documented their symptoms verbatim. ACS was eventually diagnosed in 89 (36%) women and 124 (45%) men on the basis of standard electrocardiogram and cardiac enzyme criteria. Presence of typical symptoms (chest pain or discomfort, dyspnea, diaphoresis, and arm or shoulder pain) was significantly associated with a diagnosis of ACS in women but not in men. On the other hand, atypical symptoms were not related to ACS diagnosis in women, whereas in men some atypical symptoms (dizziness or faintness) were inversely associated with ACS (P =.007). In multivariate analysis, the only symptoms that showed significant or borderline associations with ACS in women were diaphoresis (P =.019) and chest pain or discomfort (P =.069). Chest pain or discomfort and other typical symptoms were not significantly associated with ACS in men. Adjusted relative risks for ACS associated with the presence of typical symptoms in women compared with men were close to 1.0, indicating no sex differences. Conclusions: Typical symptoms are the strongest symptom predictors of ACS in women, and they are as important in women as in men. Clinicians need to take very seriously any woman who has typical symptoms and pursue a full cardiac work-up.