Protocols for dipyridamole stress testing have evolved in the last 16 years in the neverending quest of optimal diagnostic accuracy and user friendliness. Higher dipyridamole dose in a shorter infusion time provides higher sensitivity, but concern over safety is still controversial. An accelerated high-dose (0.84 mg/kg in 6 minutes without atropine) dipyridamole stress test was performed on 1,295 patients in 2 echocardiographic laborotories: Institute of Clinical Physiology of Pisa and Niguarda Hospital of Milan. During testing, there were no deaths and no patients had ventricular fibrillation. Major adverse reactions occurred in 3 cases (1 every 431 studies): 1 myocardial infarction, 1 brief cardiac asystole, and 1 transient ischemic attack. Overall feasibility was 97%. In 66 patients with normal function at rest who were evaluated off therapy, with coronary angiography performed independently of test results, the accelerated high-dose protocol showed a sensitivity of 85% (confidence interval [CI] 73% to 92%) and a specificity of 93% (CI 83% to 97%) for angiographically assessed coronary artery disease (quantitatively assessed diameter reduction > or = 50%). Diagnostic accuracy of the accelerated high dose was 89% (CI 79% to 95%). Thus, accelerated high-dose dipyridamole stress echocardiography was reasonably safe and well tolerated. This protocol is especially appealing for its excellent diagnostic accuracy coupled with the short imaging time and no need for drug cocktails.