IMPORTANCE Patients with potentially ischemic chest pain are commonly admitted to the hospital or observed after a negative evaluation in the emergency department (ED) owing to concern about adverse events. Previous studies have looked at 30-day mortality, but no current large studies have examined the most important information regarding ED disposition: the short-term risk for a clinically relevant adverse cardiac event (including inpatient ST-segment elevationmyocardial infarction, life-threatening arrhythmia, cardiac or respiratory arrest, or death). OBJECTIVE To determine the incidence of clinically relevant adverse cardiac events in patients hospitalized for chest pain with 2 troponin-negative findings, nonconcerning initial ED vital signs, and nonischemic, interpretable electrocardiographic findings. DESIGN, SETTING, AND PARTICIPANTS We conducted a blinded data review of 45 416 encounters obtained from a prospectively collected database enrolling adult patients admitted or observed with the following inclusion criteria: (1) primary presenting symptom of chest pain, chest tightness, chest burning, or chest pressure and (2) negative findings for serial biomarkers. Data were collected and analyzed from July 1, 2008, through June 30, 2013, from the EDs of 3 community teaching institutions with an aggregate census of more than 1 million visits.We analyzed data extracted by hypothesis-blinded abstractors. MAIN OUTCOMES AND MEASURES The primary outcomewas a composite of life-threatening arrhythmia, inpatient ST-segment elevationmyocardial infarction, cardiac or respiratory arrest, or death during hospitalization. RESULTS Of the 45 416 encounters, 11 230 met criteria for inclusion. Mean patient age was 58.0 years. Of the 11 230 encounters, 44.83%of patients arrived by ambulance and 55.00% of patients were women. Relevant history included hypertension in 46.00%, diabetes mellitus in 19.72%, andmyocardial infarction in 13.16%. The primary end point occurred in 20 of the 11 230 patients (0.18%[95%CI, 0.11%-0.27%]). After excluding patients with abnormal vital signs, electrocardiographic ischemia, left bundle branch block, or a pacemaker rhythm, we identified a primary end point event in 4 of 7266 patients (0.06%[95%CI, 0.02%-0.14%]). Of these events, 2 were noncardiac and 2 were possibly iatrogenic. CONCLUSIONS AND RELEVANCE In adult patients with chest pain admitted with 2 negative findings for serial biomarkers, nonconcerning vital signs, and nonischemic electrocardiographic findings, short-term clinically relevant adverse cardiac events were rare and commonly iatrogenic, suggesting that routine inpatient admission may not be a beneficial strategy for this group.