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Subjects with chest pain and a negative diagnostic workup constitute a problem for emergency physicians. We tested the usefulness of clinical variables in predicting 30-day and 6-month outcome in subjects with chest pain of undifferentiated origin after a negative workup.Chest pain of undifferentiated origin was diagnosed by negative first-line (serial electrocardiograms, troponins assays, and 12- to 24-hour observation) and second-line evaluation (echocardiography, exercise tolerance test, stress scintigraphy, stress echocardiography, coronary angiography). Thirty-day and 6-month outcomes were considered unfavorable in the presence of any of the following: death, acute coronary syndrome, need for urgent coronary revascularization. The variables considered for risk stratification were age, sex, smoking, family history of coronary artery disease, presence of hypertension, high cholesterol levels, diabetes, chronic renal failure, cerebral vascular disease, and history of acute coronary syndrome, percutaneous transluminal angioplasty (PTA), coronary artery by pass graft, and heart failure.Five items (diabetes, chronic renal failure, history of PTA or bypass, history of heart failure) were associated with 30-day unfavorable outcome (31 events/1262 cases; 2.5%). The receiver operating characteristic area of the selected items was 0.726 (95% confidence interval [CI], 0.654-0.798); sensitivity was 90.3% (73.1-95.8) and specificity was 54.8% (52.0-57.6). A similar panel of items (older age, diabetes, chronic renal failure, history of PTA) predicted an unfavorable 6-month outcome (90 subjects [7.1%], with lower accuracy (receiver operating characteristic area, 0.610 [95% CI, 0.594-0.627, P < .05]; sensitivity, 98.9% [95% CI, 93.1-99.6]; specificity, 21.6% [95% CI, 19.4-23.9]).In subjects with chest pain of undifferentiated origin, the risk of unfavorable outcome cannot be accurately predicted by the selected clinical items.