Aims <p>In patients with mitral regurgitation (MR), cardiac remodeling by two-dimensional (2D) echocardiography is variable and less suitable for individualized risk assessment. We evaluated whether three-dimensional (3D) peak LA reservoir strain (LASr) and stiffness improve risk prediction in primary MR.</p> Methods <p>In the prospective 3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation (3D-PRIME) study, 110 patients with moderate or greater primary MR underwent 2D/3D echocardiographic assessment of LASr and LA stiffness (i.e. (mitral E-wave/ annular e’ velocity)/ LASr). The primary outcome was a composite of death, heart failure worsening and mitral valve intervention.</p> Results <p>During 24 [17–26] months follow-up, the primary outcome occurred in 59 patients. In multivariable Cox analyses, low 3D LASr (HR 2.1, 95% CI 1.1–4.3) and increased 3D LA stiffness (HR 3.5, 95% CI 1.6–7.4) predicted higher risk of adverse events after adjustment for left ventricular (LV) global longitudinal strain (GLS), MR severity, LV end-systolic volume and maximum LA volume (<i>p</i> &lt; 0.05). In likelihood ratio tests, 3D LASr or LA stiffness (but not the corresponding 2D indices) increased the predictive value of a model including LV GLS and current indications for intervention in primary MR (χ² -increase from 58 to 63 / 70, <i>p</i> &lt; 0.05).</p> Conclusion <p>In moderate or greater primary MR, impaired LA function by 3D echocardiography is associated with higher risk of disease progression towards death, worsening heart failure and mitral valve intervention. Our findings lay the groundwork for future multicenter studies to explore the value of routine assessment of 3D LA remodeling in the follow-up of patients with primary MR.</p> Graphical abstract <p>3D LA strain and stiffness and clinical outcomes in primary MR</p> <p></p>