Basal left atrial volume (LAV) indexed to body surface area (LAVI) predicts adverse events in patients with organic mitral regurgitation, but information is lacking regarding change in left atrial volume during follow-up.One hundred forty-four asymptomatic patients (mean age, 71 ± 12 years; 66% women; mean ejection fraction, 66 ± 4.8%) with moderate to severe mitral regurgitation were prospectively included, with a median follow-up period of 2.76 years (interquartile range, 1.86-3.48 years).Fifty-four patients (37.50%) reached the combined end point of dyspnea and/or systolic dysfunction. Both basal and change in LAV were independently associated with the combined end point on multivariate analysis: for basal LAVI ≥ 55 mL/m(2), odds ratio, 2.26 (95% confidence interval, 1.04-4.88; P = .038), and for change in LAV ≥ 14 mL, odds ratio, 7.32 (95% confidence interval, 3.25-16.48; P < .001), adjusted for effective regurgitant orifice area and deceleration time. Combined event-free survival at 1, 2, and 3 years was significantly less in patients with basal LAVI ≥ 55 mL/m(2) (75%, 58%, and 43%) than in those with basal LAVI < 55 mL/m(2) (95%, 89%, and 77%) (log-rank test = 15.38, P = .0001). The incidence of the combined end point was highest (88%) in patients with basal LAVI ≥ 55 mL/m(2) and change in LAV ≥ 14 mL.Measurement of basal LAV and its increase during follow-up predict an adverse course in patients with moderate and severe asymptomatic mitral regurgitation. Hence, its assessment could be incorporated into the currently used algorithm for risk stratification and decision making in this group of patients.