Context: Allowing the emergency department physician to activate the cardiac catheterization laboratory is a key strategy to reduce door-to-balloon times in patients with ST-segment elevation myocardial infarction (STEMI). There are limited data on the frequency of "false-positive" catheterization laboratory activation in patients undergoing percutaneous coronary intervention for suspected STEMI. Objective: To determine the prevalence, etiology, and outcomes of false-positive cardiac catheterization laboratory activation in patients with a suspected STEMI. Design, Setting, and Patients: Prospective registry from a regional system that includes transfer of patients with STEMI from 30 community and rural hospitals with pretransfer catheterization laboratory activation for percutaneous coronary intervention at a tertiary cardiovascular center in Minnesota. A total of 1345 patients were enrolled from March 2003 to November 2006. Main Outcome Measure: Prevalence of false-positive catheterization laboratory activation in patients with suspected STEMI by 3 criteria: no culprit coronary artery, no significant coronary artery disease, and negative cardiac biomarker results. Results: Of the 1335 patients with suspected STEMI who underwent angiography, 187 (14%; 95% confidence interval [CI], 12.2%-16.0%) had no culprit coronary artery and 127 (9.5%; 95% CI, 8.0%-11.2%) did not have significant coronary artery disease. Cardiac biomarker levels were negative in 11.2% (95% CI, 9.6%-13.0%) of patients. The combination of no culprit artery with negative cardiac biomarker results was present in 9.2% (95% CI, 7.7%-10.9%) of patients. Thirty-day mortality was 2.7% (95% CI, 0.4%-5.0%) without vs 4.6% (95% CI, 3.4%-5.8%) with a culprit coronary artery (P=.33). Conclusions: The frequency of false-positive cardiac catheterization laboratory activation for suspected STEMI is relatively common in community practice, depending on the definition of false-positive. Recent emphasis on rapid door-to-balloon times must also consider the consequences of false-positive catheterization laboratory activation.