Background. Recently, NICE guidelines recommend the use of computed tomographic angiography (CTA) as the first line of investigation for new onset chest pain. We sought to evaluate the impact of the integration of CTA in the diagnostic workup, as either a first- or second-line of investigation, in the clinical practice for patients presenting with new onset chest pain, with suspicion that it may be due to coronary artery disease (CAD). Method and Results. From 2014 to 2016, 208 outpatients (mean age 63.8 ± 12.7, 37% female) with an unknown CAD diagnosis were evaluated. About half (n=106, 51%) received usual testing care plus CTA as a second-line investigation (group A), while the other half (n=102, 49%) received CTA as a first-line investigation (group B). Care decisions and test interpretations were made by the attending physician. Obstructive CAD (O-CAD) was defined as >50% stenosis in the principal branch. As determined by CTA, the rates of CAD in group A vs. group B were the following (P=0.001): 31.1% vs. 27.4% for normal/minimal CAD; 42.5% vs. 63.7% for no O-CAD; and 26.4% vs. 8.8% with O-CAD. Based on a diagnostic result of no O-CAD, invasive angiography was cancelled in 42.6% (n=45) of group A patients, and additional functional tests were cancelled for the same reason in 63.7% (n=65) of group B patients, without adverse events at median 3-year. The average diagnostic cost for patients in our study was lower in group B (206 vs. 324.42 euro; P<0.0001). Conclusions. In clinical practice, CTA, as a first- or second-line investigation, most commonly detected no O-CAD in new onset chest pain patients, leading us to safely avoid unnecessary ICA or additional functional tests. The use of CTA as a first-line investigation also appears to be cost saving, but its cost-effectiveness remains to be demonstrated in larger studies.