Background: Although conventional (CAG) and computed tomography angiography (CTA) are reliable diagnostic modalities for exclusion of obstructive coronary artery disease (CAD), they are costly and with considerable exposure to radiation and contrast media. We compared the accuracy of coronary calcium scanning (CCS) and exercise electrocardiography (X-ECG) as less expensive and non-invasive means to rule out obstructive CAD. Methods: In a rapid-access chest pain clinic, 791 consecutive patients with stable chest pain were planned to undergo X-ECG and dual-source CTA with CCS. According to the Duke pre-test probability of CAD patients were classified as low (< 30%), intermediate (30-70%) or high risk (> 70%). Angiographic obstructive CAD (> 50% stenosis by CAG or CTA) was found in 210/791 (27%) patients, CAG overruling any CTA results. Results: Obstructive CAD was found in 12/281 (4%) patients with no coronary calcium and in 73/319 (23%) with a normal X-ECG (p < 0.001). No coronary calcium was associated with a substantially lower likelihood ratio compared to X-ECG; 0.11, 0.13 and 0.13 vs. 0.93, 0.55 and 0.46 in the low, intermediate and high risk group. In low risk patients a negative calcium score reduced the likelihood of obstructive CAD to less than 5%, removing the need for further diagnostic work-up. CCS could be performed in 754/756 (100%) patients, while X-ECG was diagnostic in 448/756 (59%) patients (p < 0.001). Conclusions: In real-world patients with stable chest pain CCS is a reliable initial test to rule out obstructive CAD and can be performed in virtually all patients.