Objective: To evaluate the impact of the diagnostic test setting—inpatient versus outpatient—on adverse cardiac events (ACEs) after six months in emergency department (ED) patients with chest pain who were admitted to the hospital and subsequently had a negative evaluation for acute coronary syndrome (ACS). Methods: The authors retrospectively studied a consecutive sample of ED patients with chest pain over a nine-month period. All patients were admitted to the hospital and underwent negative evaluations for ACS, defined as the absence of diagnostic changes on serial electrocardiograms or cardiac markers (creatine kinase—MB and troponin T), and a negative diagnostic cardiac study. Subjects were classified according to cardiac diagnostic study setting—either inpatient or outpatient. Diagnostic testing included exercise treadmill, angiography, stress echocardiography, or stress thallium scans. Acute cardiac events at six months were defined as cardiac death, myocardial infarction, unstable angina, cardiac arrest, or emergent revascularization. Results: The six-month rate of ACEs among 157 subjects was 14%, with 2% cardiac mortality. The outpatient group had higher ACE risk when compared with the inpatient group using multivariate logistic regression, both for the entire cohort (OR 3.5, p < 0.03) and for a subgroup excluding patients with prior coronary artery disease (OR 6.7, p < 0.05). The outpatient group included 19 of 52 (37%) noncompliant subjects who did not receive a diagnostic study. Conclusions: Long-term cardiac morbidity of patients after a negative ACS evaluation may be higher than previously thought. Risk of ACE is significantly higher in subjects scheduled for outpatient diagnostic tests. Inpatient diagnostic testing is justified for subjects at risk for poor compliance.