ObjectivesThe addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of coronary CT angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD).MethodsThis retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACEs) during the 1-year follow-up using chi-square tests for independence. Kaplan–Meier curves were used to visualize the occurrence of safety outcomes over time.ResultsA total of 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group, and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA group, and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA), and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA, and three (2.2%) SPECT (p< 0.001 for all three options). The revascularization rate after ICA was similar between groups (p= 0.15). However, patients in the CCTA group more often underwent revascularization (p= 0.007).ConclusionAddition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after 1 year.Key Points•Previous studies have shown that computed tomography–derived fractional flow reserve improves the accuracy of coronary computed tomography angiography without changes in acquisition protocols.•This study shows that use of computed tomography-derived fractional flow reserve as gatekeeper to invasive coronary angiography in patients suspected of stable coronary artery disease leads to less invasive testing and revascularization without observed difference in outcomes after 1 year.•This could lead to a significant reduction in costs, complications and (retrospectively unnecessary) usage of diagnostic testing capacity, and a significant increase in patient satisfaction.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00330-023-09517-z.