Purpose: Exercise ECG (ExECG) is widely used to assess patients with suspected coronary artery disease (CAD). However stress echocardiography (SE) is a well-established alternative technique for the assessment of these patients. We hypothesised that SE, due to its greater accuracy and feasibility, may be superior to ExECG, in terms of positive predictive value and cost effectiveness, when used as the initial test for the assessment of patients with no previous history of CAD presenting with suspected stable angina. Methods: Patients referred with recent onset chest pain during 2011, with no known history of CAD and with a pre-test likelihood of CAD greater than 10%, who underwent first line ExECG or SE were identified. The tests were classified as positive, negative or inconclusive for ischaemia. Coronary angiography (CA) was performed, with the knowledge of the functional test results, as indicated clinically. CAD was defined as the presence of >50% stenosis in at least one major epicardial vessel on CA. Cost to diagnosis of CAD was determined for each functional test by adding the initial cost, of the test to the cost of subsequent tests leading to and including CA. Follow up data on hard events, cardiac death and acute myocardial infarction (AMI), were collected on all patients for a period up to one year after the presentation of the last study patient. Results: We identified 457 patients who underwent ExECG (225 (49%) negative, 94 (21%) positive, 138 (30%) inconclusive) and 257 who underwent SE (213 (83%) negative, 38 (15%) positive, 6 (2%) inconclusive) as first line. The mean pre-test probability of CAD was 43±26% vs 51±28% respectively. Of 74 patients referred for CA on the basis of ExECG, CAD was present in 35 (47%) which was significantly (p=0.04) lower than in the SE group which predicted CAD in 28 out of 42 patients referred for CA (67%). The mean cost to diagnosis was £460 for the ExECG versus £385 for the SE group (p=0.02). No cardiac deaths were found in either group. There was no difference in event rate, (p=0.8 by log rank test) of AMI in patients who were discharged on the basis of a negative ExECG (4 (2%)) versus those with a negative SE (4 (2%)) over a period of 18±6 months. Conclusions: In a population with intermediate pre-test probability of CAD, SE was more accurate and more cost effective for predicting the presence of CAD compared to ExECG. This study suggests that SE rather than ExECG should be the initial test for the assessment of suspected stable angina in this population.