Objectives Previous studies showed that subclinical abnormal left atrial (LA) function could be diagnosed with LA speckle tracking evaluation long before chamber enlargement. Osteoprotegerin (OPG) is a member of the tumor necrosis factor (TNF) receptor superfamily and was recently found to be an indicator for adverse cardiovascular outcomes and a risk factor for new onset atrial fibrillation. The authors hypothesized that OPG values could predict LA mechanical dysfunction and LA remodeling assessed by two-dimensional speckle tracking echocardiography (2D-STE) in patients with hypertension (HT) and diabetes mellitus (DM). Methods A single center study was conducted including consecutive patients presenting to the authors' outpatient clinic. Enrolled patients needed to have been treated for HT and DM for at least 1 year. Results The study included 80 patients (mean age, 57.5 & x202f;+/- 8.3 years). Patients in the impaired LA strain group were older (p & x202f;= 0.035), had lower low density lipoprotein (LDL) cholesterol (mg/dl) (p & x202f;= 0.021), and higher OPG (pmol/l) (p & x202f;= 0.004) values than patients in the normal LA strain group. Univariate logistic regression analysis demonstrated that age (p & x202f;= 0.039), LDL cholesterol (mg/dl) (p & x202f;= 0.025), and OPG (pmol/l) (p & x202f;= 0.008) values were associated with impaired LA strain. Backward multivariate logistic regression analysis showed that LDL cholesterol (mg/dl) (OR: 0.982, CI 95% 0.964-0.999,p & x202f;= 0.049) and OPG (pmol/l) (OR: 1.438, CI 95% 1.043-1.983,p & x202f;= 0.027) were independently associated with impaired LA strain. Conclusion In hypertensive and diabetic patients, higher OPG values were associated with impaired LA function assessed by 2D-STE. In this high-risk patient group, serum OPG can be used as a risk predictor for LA mechanical dysfunction.