Background-Global longitudinal strain (GLS) is prognostic of adverse cardiovascular outcomes in various patient populations, but the prognostic utility of GLS for long-term cardiovascular morbidity and mortality in the general population is unknown. Methods and Results-A total of 1296 participants in a general population study underwent a health examination, including echocardiography measurement of GLS. The primary end point was the composite of incident heart failure, acute myocardial infarction, or cardiovascular death. During a median follow-up of 11 years, 149 (12%) participants were diagnosed with heart failure, acute myocardial infarction, or cardiovascular death. Lower GLS was associated with a higher risk of the composite end point (hazard ratio, 1.12; 95% confidence interval, 1.08-1.17; P<0.001 per 1% decrease), an association that persisted after multivariable adjustment for age, sex, heart rate, hypertension, systolic blood pressure, left ventricular ejection fraction, left ventricular mass index, left ventricular dimension, deceleration time, left atrium dimension, E/e′, and pro B-type natriuretic peptide (hazard ratio, 1.05; 95% confidence interval, 1.00-1.11; P=0.045 per 1% decrease). GLS provided incremental prognostic information beyond the Framingham Risk Score, the Systemic Coronary Evaluation risk chart, and the modified American College of Cardiology/American Heart Association Pooled Cohort Equation for the composite outcome and incident heart failure. Sex modified the relationship between GLS and outcome such that after multivariable adjustment, GLS was an independent predictor of outcomes in men but not in women (hazard ratio, 1.14; 95% confidence interval, 1.06-1.24; P=0.001, and hazard ratio, 0.99; 95% confidence interval, 0.92-1.07; P=0.81, respectively; P for interaction =0.032). Conclusions-In the general population, GLS provides independent and incremental prognostic information regarding long-term risk of cardiovascular morbidity and mortality. GLS seems to be a stronger prognosticator in men than in women.