The aims of this prospective, observational study were to compare: (1) symptom presentation of coronary heart disease (CHD) between patients with and without diabetes and (2) symptom predictors of CHD in patients with and without diabetes. We directly observed 528 patients with symptoms suggestive of CHD as they presented to the ED of a 900-bed cardiac referral center in the northeastern United States. There were no significant differences in symptom presentation of CHD between patients with and without diabetes, although patients with diabetes were slightly more likely to present with shortness of breath (P =.056). Patients with diabetes reported their symptoms to be more severe compared with those without diabetes (P =.036). Neck/throat pain and arm/shoulder pain were of borderline significance in predicting CHD in patients with diabetes (P =.059 and P =.052, respectively). Classic chest symptoms and diaphoresis were independent predictors of CHD in patients without diabetes (P =.002 and P =.049, respectively). The perceived severity of symptoms was not predictive of CHD in patients with or without diabetes. Symptoms thought to be diagnostic of CHD are not helpful in patients with diabetes. Future research should focus on identifying more useful predictors of CHD in patients with diabetes.