OBJECTIVE: Risk assessment is important in determining the management of patients with suspected or confirmed coronary artery disease (CAD). However, evidence supporting the clinical impact of contrast echocardiography (CE) in this sphere is not well known. The objective was to review and summarise the clinical data for licensed and investigational applications of CE in CAD, using systematic review methodology. METHODS: Full publications of clinical studies of selected contrast agents were identified through searches of electronic literature databases and application of predefined inclusion criteria. Studies were categorised and key data were extracted and tabulated for analysis. No statistical pooling of data was undertaken due to study heterogeneity. RESULTS: 2,275 abstracts were screened. 61 studies met inclusion criteria and were categorised as follows: effectiveness in image enhancement (23 studies); accuracy in the diagnosis of CAD, using coronary angiography as the diagnostic gold standard (23 studies); myocardial viability assessment (16 studies); prognostic accuracy (2 studies). Using second generation contrast agents, diagnostic images were obtained in 48-98% (median=74%) of patients with suboptimal un-enhanced images and several studies reported improved intra- and inter-operator reproducibility. Reported sensitivities and specificities for CAD diagnosis ranged from 41-100% (median=86%) and 44-100% (median=81%). Two studies reported that information gained from myocardial contrast echocardiography (MCE) provided incremental diagnostic value to that from left ventricular function (LVF) assessment alone. Reported sensitivities and specificities of myocardial viability assessment by MCE for predicting LVF recovery ranged from 50-96% (median=74%) and 44-96% (median=83%). CONCLUSIONS: The body of evidence suggests that effective use of contrast agents in echocardiography extends beyond the licensed use in patients with suboptimal baseline images. MCE is effective in the assessment of myocardial perfusion in the diagnosis of CAD and the detection of myocardial viability. Interpretation is limited by the size of studies, lack of long-term outcomes and potential referral bias.