Background Patients with mild to moderate aortic stenosis (AS) seem to have a worse outcome than commonly expected. Early identification of subjects who may develop a rapid disease progression or cardiovascular events is critical in order to apply adequate risk management. Study design Observational prospective single-centre study. Objective To determine the prognostic role of exercise stress echocardiography (ESE) in patients with mild and moderate asymptomatic AS. Patients Ninety consecutive patients (mean age 74 ± 12 years) with isolated mild and moderate AS were enrolled into the study protocol over a 20 months period. Follow-up time was 12 months. Methods A complete echocardiographic study with tissue Doppler imaging (TDI) was performed at baseline and during semi-supine symptom-limited exercise test to evaluate: (1) the occurrence of symptoms, (2) ST segment changes, (3) transaortic pressure gradient, (4) the E/A ratio, (5) the E/e′ ratio and (6) the systolic pulmonary artery pressure. Main outcome measures During the 1 year follow-up time, we evaluated the occurrence of adverse cardiac events, defined as any of the following: (1) cardio-vascular hospitalization; (2) requirement for aortic valve replacement; (3) cardiac death. Results During follow-up, three patients died, 11 underwent aortic valve replacement and 26 had cardiovascular hospitalizations. On univariate analysis, patients who exhibited symptoms during exercise (HR 2.93, p = 0.003); the occurrence of a ≥2 mm exercise-induced ST segment depression (HR 3.12, p = 0.001); a ≥15 mmHg increase in mean transaortic pressure gradient during exercise (HR 2.77, p = 0.001); a ≥50 mmHg exercise-induced increase in systolic pulmonary artery pressure (HR 2.90, p = 0.009); an exercise-induced pseudo-normalization of the E/A ratio (E/A ≥ 1) (HR 7.50, p = 0.0001) and, particularly, a ≥15 exercise-induced increase in the E/e′ ratio (HR 7.69, p = 0.0001) had a significantly higher risk of cardiac events during the follow-up time. On multivariate analysis, only the latter covariate (HR 6.04, p = 0.009) was independently associated with adverse cardiac events. Conclusions A ≥15 stress-induced increase in E/e′ ratio is highly predictive of cardiac events in patients with mild to moderate AS. Assessment of diastolic function using TDI during ESE provides additional prognostic information in such patients.