An increase in the ploidy of cardiomyocytes (CMCs) determines the potential for their hypertrophic growth. We analyzed the changes in CMC ploidy and size of the interventricular septum in patients with hypertrophic cardiomyopathy (HCM) and tetralogy of Fallot (TF). The ploidy of CMCs in children and adult patients with HCM and children with TF was 1.5-2-fold higher than in individuals without cardiovascular pathology, and it did not change with age. The size of the CMCs was also larger by 1.3-2 times in patients with HCM and TF, compared to the control groups. However, the increase in CMCs size was more significant in HCM than in TF. The proportion of multinucleated CMCs was significantly lower in patients with HCM compared to controls and was by almost 2 times higher in patients with TF. Thus, myocardial hypertrophy in HCM is mainly due to the polyploidy of mononucleated CMCs, whereas in TF, the proportion of multinucleated CMCs increases.