Aims: The aim of the study was to assess the additive prognostic value of coronary flow velocity reserve (CFVR) alongside wall motion analysis during exercise echocardiography in patients with known or suspected coronary artery disease (CAD). Methods and results: In a prospective, single-centre, observational study, we evaluated 689 patients (449 males; 56 + 9 years) who underwent supine bicycle stress echo (ESE) with CFVR evaluation of the left anterior descending artery (LAD) by Doppler. ESE was positive for regional wall motion abnormalities in 359 (52%) patients. Mean CFVR was 1.9 ± 0.8. During a median follow-up of 36.6 months, there were 200 patients with major adverse cardiac events (MACE): 15 deaths, 17 non-fatal myocardial infarctions [11 of them also had percutaneous coronary intervention with stenting (PCI) or/and coronary artery bypass graft surgery (CABG)] and 179 patients underwent revascularization. The 37 months' event-free survival showed the best outcome for those patients with negative ESE by wall motion criteria and normal CFVR, and the worst outcome for patients with positive ESE by wall motion and abnormal CVFR (99 vs. 42%, P < 0.0001). At multivariable analysis, CFVR in LAD (OR 0.53, 95% CI 0.35-0.79, P < 0.0001), positivity for regional wall motion abnormalities during testing (OR 0.10, 95% CI 0.04-0.25, P < 0.000), previous PCI (OR 0.38, 95% CI 0.16-0.90, P < 0.003), male sex (OR 0.44, 95% CI 0.27-0.71, P < 0.0009), and heart rate reached during exercise (OR 0.98, 95% CI 0.96-0.99, P < 0.02) were independent prognostic predictors of MACE. Conclusion: In patients with known or suspected CAD, exercise stress tests measuring wall motion criteria and CFVR are additive and complementary for the identification of patients at risk of experiencing major adverse events.