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Studies have identified sex differences in symptoms of acute coronary syndrome (ACS); however, retrospective designs, abstraction of symptoms from medical records, and variations in assessment forms make it difficult to determine the clinical significance of sex differences.The aim of this study is to determine the influence of sex on the occurrence and distress of 13 symptoms for patients presenting to the emergency department for symptoms suggestive of ACS.A total of 1064 patients admitted to 5 emergency departments with symptoms triggering a cardiac evaluation were enrolled. Demographic and clinical variables, symptoms, comorbid conditions, and functional status were measured.The sample was predominantly male (n = 664, 62.4%), white (n = 739, 69.5%), and married (n = 497, 46.9%). Women were significantly older than men (61.3 ± 14.6 vs 59.5 ± 13.6 years). Most patients were discharged with a non-ACS diagnosis (n = 590, 55.5%). Women with ACS were less likely to report chest pain as their chief complaint and to report more nausea (odds ratio [OR], 1.56; confidence interval [CI], 1.00–2.42), shoulder pain (OR, 1.76; CI, 1.13–2.73), and upper back pain (OR, 2.92; CI, 1.81–4.70). Women with ACS experienced more symptoms (6.1 vs 5.5; P = .026) compared with men. Men without ACS had less symptom distress compared with women.Women and men evaluated for ACS reported similar rates of chest pain but differed on other classic symptoms. These findings suggest that women and men should be counseled that ACS is not always accompanied by chest pain and multiple symptoms may occur simultaneously.