Background The prognostic value of coronary CT angiography (CTA)-derived quantitative flow ratio (CT-QFR) remains unknown. Purpose To determine the prognostic value of CT-QFR in predicting the long-term outcomes of patients with suspected coronary artery disease (CAD) in comparison with invasive coronary angiography (ICA)/SPECT and to determine the influence of prior percutaneous coronary intervention (PCI) on the prognostic value of CT-QFR. Materials and Methods In this secondary analysis of the prospective international CORE320 study, 379 participants who underwent coronary CTA and SPECT within 60 days before ICA between November 2009 and July 2011 were included for follow-up. The coronary CTA images were analyzed to determine CT-QFR. The primary outcome was major adverse cardiovascular events (MACEs) in the 5-year follow-up. Kaplan-Meier curves, multivariable Cox regression models adjusted for clinical variables, and areas under the receiver operating characteristic curves (AUCs) were used to assess and compare the predictive ability of CT-QFR and ICA/SPECT. Results CT-QFR computation and 5-year follow-up data were available for 310 participants (median age, 62 years), of whom 205 (66%) were male. CT-QFR (hazard ratio, 1.9 [95% CI: 1.0, 3.5]; P = .04) and prior myocardial infarction (hazard ratio, 2.5 [95% CI: 1.5, 4.0]; P < .001) were independent predictors of MACE occurrence in the 5-year follow-up. MACE-free survival rates were similar in participants with normal CT-QFR and ICA/SPECT (82% vs 80%; P = .45) and in participants with abnormal CT-QFR and ICA/SPECT findings (60% vs 57%; P = .40). In participants with prior PCI, CT-QFR had a lower AUC in predicting MACEs than in participants without prior PCI (0.44 vs 0.70; P < .001). Conclusion CT-QFR was an independent predictor of MACEs in the 5-year follow-up in participants with suspected CAD and showed similar 5-year prognostic value to ICA/SPECT; however, prior PCI affected CT-QFR ability to predict MACEs. Clinical trial registration no. NCT00934037 © RSNA, 2024 Supplemental material is available for this article.