Background: Although conventional coronary angiography is the gold standard tool of diagnosing coronary artery disease (CAD), it is an invasive procedure, and it can miss non-coronary causes of acute chest pain. Triple role out CT has emerged as a promising tool for assessment of such cases. Herein, we present our experience in comparing “triple out CT" as a diagnostic tool for acute chest pain patients. Objective: The aim of the current study was to assess the validity and efficacy of triple rule-out CT in diagnosis of different vascular causes of chest pain in the Emergency Department. Patients and methods: The data of 50 patients with an intermediate risk for CAD were retrospectively reviewed. All of them underwent the triple out protocol, and when coronary cause was established, conventional angiography was done. Results: CT angiography (CTA) revealed CAD in 29 (58%) subjects, while non-coronary disease was detected in 12 (24%) patients. The remaining nine subjects had negative CTA study. In the patients diagnosed with CAD, most of them had severe disease (82.8%), whereas the remaining five patients had moderate one. Findings rather than CAD included pulmonary embolism, mediastinal mass, acute aortic disease, pulmonary disease, hernia, and pulmonary artery aneurysm. There was a significant relation agreement between CTA and cardiac catheterization regarding the severity of CAD (P<0.001). Conclusion: Triple out CT could be a surrogate diagnostic modality for patients with acute chest pain, even when CAD is suspected. It can yield comparable results compared to the conventional coronary angiography. Therefore, its application is widely recommended in low-source emergency settings.