Dobutamine-atropine stress echocardiography (DASE) is an established method and has been shown to be accurate for the detection of coronary artery disease. Still, there are few large clinical studies that analyze the safety of DASE in general or the safety of performing it on an ambulatory basis. Most studies use a target heart rate as the primary end point regardless of whether asymptomatic ischemia occurs. Such studies have shown a serious cardiac event rate of approximately 0.3%. We prospectively studied 4,033 consecutive patients on an ambulatory basis and in the hospital with the use of DASE from July 1991 to December 1998. All tests were performed by an experienced physician, and all clinical and DASE data were stored in a large database organized at the beginning of the study. Dobutamine was infused in scalar doses of 5, 10, 20, 30, and 40 microg/kg per minute in 3-minute stages. Development of a new wall motion abnormality, achievement of 85% of target heart, and end of the DASE infusion protocol were used as an end point. If 85% of the target heart rate was not achieved, atropine was infused up to 1 mg in the absence of myocardial ischemia, which was used in 1,280 studies. There were 3,645 diagnostic tests, and 388 (10%) were found to be nondiagnostic. This result was due to poor image quality in 115 (3%), end of protocol in negative-submaximal examinations in 124 (3%), and limiting side effects in 149 (4%). Thirty-seven percent of the tests showed positive results for myocardial ischemia. Major test-related cardiac complications occurred in 10 (0.25%) patients and included 1 ventricular fibrillation, 1 case of myocardial infarction, and 8 cases of sustained ventricular tachycardia. Atropine poisoning was observed in 5 (0.12%) patients. No deaths occurred as a direct or indirect consequence of DASE. We conclude that dobutamine-atropine stress echocardiography is a reasonably safe method for detection of coronary artery disease in the hospital or in an ambulatory basis. The use of new wall motion abnormality as 1 of the end points may prevent further ischemia-related complications.