This study explores gender differences in symptom presentation associated with coronary heart disease (CHD). In this prospective study, nurse data collectors directly observed 550 patients as they presented to the Emergency Department (ED) of Yale-New Haven Hospital. The final sample included 217 patients (41% women) diagnosed with CHD (acute coronary ischemia or myocardial infarction). Chest pain was the most frequently reported symptom in women (70%) and men (71%). Unadjusted analyses revealed that women were more likely than men to present with midback pain (odds ratio [OR] 9.61, 95% confidence interval [CI] 2.10 to 44.11, p = 0.001), nausea and/or vomiting (OR 2.29, 95% CI 1.19 to 4.42, p = 0.012), dyspnea (OR 1.82, 95% CI 1.05 to 3.16, p = 0.032), palpitations (OR 3.42, 95% CI 1.02 to 11.47, p = 0.036), and indigestion (OR 2.13, 95% CI 1.03 to 4.44, p = 0.040). After adjustment for age and diabetes, women were more likely to present with nausea and/or vomiting (OR 2.43, 95% CI 1.23 to 4.79, p = 0.011) and indigestion (OR 2.13, 95% CI 1.10 to 4.53, p = 0.048). Women (30%) and men (29%) were equally likely to present without chest pain, and dyspnea was the most common non-chest pain symptom. In the subgroup of patients without chest pain, unadjusted analyses revealed that women were more likely to report nausea and/or vomiting compared with men (OR 4.40, 95% CI 1.30 to 14.84, p = 0.013). Although we found some significant gender differences in non-chest pain symptoms, we conclude that there were more similarities than differences in symptoms in women and men presenting to the ED with symptoms suggestive of CHD who were later diagnosed with CHD.