That European researchers consistently find a prevalence of PE of > 20%, compared with the 5 to 10% observed in the United States, has previously provoked dialogues similar to this one.2–4 Several reasons explain this difference in prevalence. First, our sample was truly consecutive with virtually no missed subjects, such that we included even the lowest of low-suspicion workups, as long as the patient had a d-dimer test ordered for the purpose of excluding PE. Our research protocol played no role in the physicians’ decisions to order a d-dimer test. Second, when compared with the health-care system in the United States, the European health-care system enjoys a more functional primary care network, affording the opportunity for physician referral of many of the patients who are evaluated for PE in European emergency departments (EDs). Therefore, these partially prescreened populations who are evaluated for PE in European EDs should ostensibly have a higher underlying prevalence of PE compared with those in the United States. In urban America, emergency physicians evaluate an almost entirely unscreened population. Very few of our patients have reliable access to a primary care physician. Most patients have no choice except to visit the ED when they seek medical evaluation for symptoms such as chest pain or shortness of breath (or “breathing difficulties”). Finally, following hospital discharge, most of our patients are unable to access a physician if they have continued symptoms. As a result, the careful and diligent emergency physician in urban America must test liberally for PE, leading to a low prevalence. Indeed, approximately 3% of the 115,000 patients whom we care for each year in our own ED receive some type of diagnostic test for PE. In this setting, a rapid and safe point-of-care diagnostic test for PE remains an unmet imperative.