Objectives. The purpose of this study was to determine the safety of adenosine infusion at 140 μg/kg per min in conjunction with radionuclide imaging in 9,256 consecutive patients. Background. Adenosine produces maximal myocardial hyperemia directly with a rapid onset of action. In addition, when used in conjunction with radtonuclide perfusion imaging, it has proven efficacy for the diagnosis of coronary artery disease in patients unable to exercise. Because the ultrashort half-life (<10 s) allows dose titration and rapid reversal of side effects, it may be safer than other available pharmacologic agents. Methods. Patients were prospectively entered at 21 clinical sites. Information on safety and adverse events during and immediately after adenosine infusion was maintained in the Adenoscan Multicenter Trial Registry. Results. The infusion protocol was completed in 80% of patients, required dose reduction in 13% and was terminated early in 7%. Interpretable imaging studies were obtained in 98.7% of patients, and 0.8% of patients received aminophylline. Minor and well tolerated side effects were reported in 81.1% of patients. There were no deaths, one myocardial infarction, seven episodes of severe bronchospasm and one episode of pulmonary edema. Transient atrioventricular (AV) node block occurred in 706 patients (first-degree in 256, second-degree in 378 and third-degree in 72) and resolved spontaneously in most patients (n = 508) without alteration in the adenosine infusion. There were no sustained episodes of AV block. Patients >70 years of age had an increased risk of developing AV block (age <70,7.05% vs. ≥ 70, 9.44%, p = 0.001, relative risk 1.37). Conclusions. Adenosine infusion is safe. Vasodilator and negative dromotropic side effects are generally well tolerated. Serious side effects are relatively rare, and they reverse with termination of adenosine infusion. Interpretable radionuclide studies were obtained in 98.7% of patients and aminophylline reversal was seldom required. © 1994.