Study objective Coronary computed tomographic (CT) angiography has excellent performance characteristics relative to coronary angiography and exercise or pharmacologic stress testing. We hypothesize that coronary CT angiography can identify a cohort of emergency department (ED) patients with a potential acute coronary syndrome who can be safely discharged with a less than 1% risk of 30-day cardiovascular death or nonfatal myocardial infarction. Methods We conducted a prospective cohort study at an urban university hospital ED that enrolled consecutive patients with potential acute coronary syndromes and a low TIMI risk score who presented to the ED with symptoms suggestive of a potential acute coronary syndrome and received a coronary CT angiography. Our intervention was either immediate coronary CT angiography in the ED or after a 9- to 12-hour observation period that included cardiac marker determinations, depending on time of day. The main clinical outcome was 30-day cardiovascular death or nonfatal myocardial infarction. Results Five hundred sixty-eight patients with potential acute coronary syndrome were evaluated: 285 of these received coronary CT angiography immediately in the ED and 283 received coronary CT angiography after a brief observation period. Four hundred seventy-six (84%) were discharged home after coronary CT angiography. During the 30-day follow-up period, no patients died of a cardiovascular event (0%; 95% confidence interval CI 0% to 0.8%) or sustained a nonfatal myocardial infarction (0%; 95% CI 0 to 0.8%). Conclusion ED patients with symptoms concerning for a potential acute coronary syndrome with a low TIMI risk score and a nonischemic initial ECG result can be safely discharged home after a negative coronary CT angiography test result.