Context: The most frequent cause of death in acromegaly is cardiomyopathy. Objective: To evaluate determinants of acromegalic cardiomyopathy. Design: Observational, open, controlled, retrospective study. Subjects: Two hundred and five patients with newly diagnosed active acromegaly (108 women and 97 men; median age 44 years) and 410 non-acromegalic subjects sex-and age-matched with the patients. Main outcome measures: Left ventricular (LV) mass index (LVMi), transmitral inflow early-to-atrial (E/A) peak velocity ratio, and LV ejection fraction (LVEF) were measured by Doppler echocardiography to determine the prevalence of LV hypertrophy (LVH), diastolic and systolic dysfunction. The role of age, estimated disease duration, body mass index, GH and IGF1 levels, systolic and diastolic blood pressure, lipid profile and glucose tolerance in determining different features of the acromegalic cardiomyopathy was investigated. Results: Compared with controls, the patients had lower E/A, LVEF, high-density lipoprotein (HDL)-cholesterol levels and higher LVMi, total-and low-density lipoprotein (LDL)-cholesterol, triglycerides, glucose and insulin levels, homeostatic model assessment of insulin resistance (HOMA-R) and HOMA-b. The relative risk to develop mild (odds ratio (OR)Z1.67 (1.05-2.66); PZ0.027) or severe hypertension (ORZ1.58 (1.04-2.32); PZ0.027), arrhythmias (ORZ4.93 (1.74-15.9); PZ0.001), impaired fasting glucose/impaired glucose tolerance (ORZ2.65 (1.70-4.13); P!0.0001), diabetes (ORZ2.14 (1.34-3.40); PZ0.0009), LVH (ORZ11.9 (7.4-19.5); P!0.0001), diastolic (ORZ3.32 (2.09-5.31); P!0.0001) and systolic dysfunction (ORZ14.2 (6.95-32.2); P!0.0001), was higher in acromegaly. The most important predictor of LVH (tZ2.4, PZ0.02) and systolic dysfunction (tZK2.77, PZ0.006) was disease duration and that of diastolic dysfunction was patient's age (tZK3.3, PZ0.001). Patients with an estimated disease duration of O10 years had a relative risk to present cardiac complications three times higher than patients with estimated disease duration %5 years. Conclusions: The prevalence of different features of cardiomyopathy is 3.3-14.2 times higher in the acromegalic than in the non-acromegalic population. The major determinant of cardiomyopathy is disease duration.