Background: Regional apical longitudinal strain can corroborate the diagnosis of regional wall motion abnormalities on a quantitative basis, but data on long-term prognostic value are lacking.Objectives: To evaluate the physiological correlate and the prognostic value of apical longitudinal strain versus wall motility during dipyridamole stress echocardiography.Methods: Retrospective study, which included 150 patients referred for dipyridamole stress echocardiography. Apical longitudinal strain, anterior descending artery coronary reserve, and visual analysis of wall motility were evaluated. Patients were divided into two groups. Group 1: patients with normal apical longitudinal strain, and Group 2: abnormal strain. Follow-up was carried out for 36 ± 9.3 months. Major event was defined as: death, myocardial infarction, revascularization and hospitalizationfor cardiac causes.Results: Eighty-seven patients (61.3%) in Group 1 and 55 (38.7%) patients in Group 2 were included (8 patients were excluded due to a suboptimal ultrasound window). There were no differences in apical longitudinal strain at rest between the groups.During the stress, Group 1 patients showed better visual wall motility and a higher coronary reserve (p < 0.001). The coronary reserve showed a linear correlation with the changes in the apical longitudinal strain (Pearson’s correlation coefficient 0.89, p < 0.0001). At follow-up, there were 24 major events. Group 1 patients had better event-free survival (p < 0.01) andapical longitudinal strain proved to be a better independent event predictor than wall motion analysis (p = 0.002 vs p = 0.1) in logistic regression analysis.Conclusions: Apical longitudinal strain has a very good correlation with physiological standards –coronary flow velocity reserve–and its association with long-term prognosis is better. Abnormal apical longitudinal strain during dipyridamole stress echocardiography predicted a worse outcome, regardless of visual wall motion analysis. How to cite this article: Lowenstein Haber D, Arbucci R, Amor M, Merlo P, Saad A, Lowenstein JA. Pathophysiology and Prognosis of Apical Longitudinal Strain During Dipyridamole Stress Echocardiography. Rev Argent Cardiol 2022;90:92-8. http://dx.doi.org/10.7775/rac.v90.i2.20502