This study examines the question of whether chest pain observation units increase the proportion of chest pain patients with an extended evaluation for cardiac ischemia (“rule out myocardial infarction [MI] evaluation”), decrease the number of missed MIs, and decrease costs. This is a multiple site registry study of 8 established chest pain observation units (complying with the American College Emergency Physician’s Observation Section’s standards) compared with previous studies on chest pain evaluation without the use of observation (5 studies, 12,405 patients). A total of 23,407 of 444,189 emergency department patients (5.3%) had the chief complaint of chest pain during the study period. In the chest pain observation units, 153 of 2,229 patients (6.9%) with acute MI were identified. Most of the observation chest pain patients (76%) were discharged home without hospital admission. Compared to previous studies, a higher proportion of patients underwent a “rule out MI evaluation” (67%, 95% confidence interval [CI] 66%, 68% vs 57%, 95% CI 56%, 58%; p <0.001) equal to 2,250 additional patients completely evaluated ($1,219,500 additional costs). A lower proportion of MIs were missed (0.4%, 95% CI 0.3%, 0.5% vs 4.5%, 95% CI 4.0% to 5.5%; p <0.001) as estimated by return visits within 72 hours. Compared to previous studies, final hospital admission rate was lower (47%, 95% CI 46%, 48% vs 57%, 95% CI 56%, 58%; p <0.001), equal to 2,314 hospital admissions avoided in the study population ($4,093,466 saved costs). Calculated true costs overall were lower by $2,873,966 at the study hospitals. Thus, chest pain observation units increased the proportion of chest pain patients thoroughly evaluated with improved quality of care and lower costs.