Myocardial contrast echocardiography has the potential to accurately detect functionally significant coronary artery disease during pharmacologic stress testing. Different low-mechanical index modalities, including triggering replenishment imaging (TRI) and real-time imaging (RTI), are currently used to identify myocardial perfusion defects. We compared the ability of TRI with that of RTI for detecting and localizing perfusion abnormalities. Thirty-six patients (62 ± 14 years old, 15 men) underwent single-photon emission computed tomography (SPECT) with technetium-99m sestamibi and myocardial contrast echocardiography at baseline and after infusion of 0.56 mg/kg of dipyridamole. Sixteen of these patients also underwent quantitative angiography. Contrast-enhanced images were obtained in 4-, 3-, and 2-chamber views after intravenous bolus injections of lipid-encapsulated microbubbles (0.1 ml of Definity). A myocardial perfusion defect was defined by myocardial contrast echocardiography as a delay of >2 seconds in contrast replenishment after high-mechanical index flash impulse. The myocardial segments were divided into 3 major coronary territories. There was agreement in detecting perfusion defects between SPECT and TRI in 26 patients (72%, κ = 0.46) and between SPECT and RTI in 27 patients (75%, κ = 0.50). Agreements between myocardial contrast echocardiography and SPECT for localizing coronary territories with perfusion defects were 81% for TRI (κ = 0.43) and 85% for RTI (κ = 0.61). Accuracy of RTI for detecting >50% diameter stenoses by quantitative angiography was 79%, that of TRI was 71%, and that of SPECT was 65%. These data indicate that the different low-mechanical index imaging schemes are equivalent to radionuclide SPECT in accurately detecting diseased coronary artery territories during vasodilator stress.