Background: The aim of the present study was to describe the morphological changes in the normal pattern of ventricular myoarchitecture in the prenatal and adult human heart, to understand the three‐dimensional organization of the muscle fibers and their active functional role in valvular dynamics. Methods: We used dissection and histological techniques in 56 human hearts from fetuses and adults of both sexes. Results: In all hearts, the ventricular wall was arranged in three different layers: superficial (subepicardial), middle, and deep (subendocardial) myocardium. The superficial and deep layer are present in both ventricles, whereas the middle layer is found only in the left ventricle. Age‐related differences were noted in the pattern of myoarchitecture of the superficial layer, mainly in the fetal period, and especially in the right ventricle; however, the middle layer always shows a circumferential pattern, which is specially evident in elderly hearts. The ventricular fibers in the superficial and deep layers are anchored in the ventricular orifices. Conclusions: Our findings reveal that muscle fiber architecture showed age‐but not sex‐related differences. These variations may reflect a mechanism of adaptation of the heart to functional demands throughout life. © 1995 Wiley‐Liss, Inc.