Aims: Dobutamine-gated SPECT imaging allows simultaneous perfusion and function assessment and is an alternative stress method for evaluating coronary artery disease in patients unable to perform treadmill exercise. In some patients, a paradoxical decrease in heart rate has been observed during high dose dobutamine infusion. The purpose of this study was to describe the paradoxical decrease in heart rate observed during dobutamine perfusion scintigraphy and determine its relation to inducible ischemia and angiographic coronary artery disease. Methods and Results: We studied 52 patients who underwent dobutamine-gated <sup>99m</sup>Tc sestamibi SPECT imaging and coronary angiography within 30 days. Paradoxical deceleration was defined as a decrease in heart rate ≥5 beats/min lasting at least 3 min during dobutamine infusion. Perfusion was graded on a five-point scale (0 = normal; 4 = absent uptake) and wall motion on a four-point scale (0 = akinesia/dyskinesia; 3 = normal) using the 20-segment model. Significant coronary artery disease was defined as ≥50% narrowing of lumen diameter of a major epicardial artery. Paradoxical deceleration occurred in 10 patients (19%, 95% CI 8–30%). A decrease in systolic blood pressure [8 patients (80%), 95% CI 56–92%] with angina [5 patients (50%), 95% CI 23–71%] often accompanied the decrease in heart rate. All 10 patients with sinus deceleration had an inferior wall perfusion defect and 8 of them had a corresponding wall motion abnormality on gated images. Significant coronary artery disease was present in all 10 patients with sinus deceleration, with an increased incidence of right coronary artery stenosis (p = 0.007). Conclusions: Paradoxical deceleration observed during dobutamine perfusion scintigraphy is associated with inducible ischemia and angiographic coronary artery disease and the underlying mechanism for this phenomenon may be the activation of the Bezold-Jarisch reflex.