Paper description: • Clarification of the effects of levothyroxine treatment on cardiovascular risk present in subclinical hypothyroidism may contribute to the strategy in planning cardiovascular preventive treatments. • We examined whether treatment of subclinical hypothyroidism by levothyroxine has any effect on cardiac morphology and function estimated by standard electrocardiographic and echocardiographic indicators. • Our results suggest a subtle improvement of cardiac structure and function. • The study supports electrocardiographic and echocardiographic evaluation for monitoring the therapeutic effect of levothyroxine. This could also be an objective approach when deciding whether a patient should be treated permanently after the trial period. Abstract: Current controversies related to the treatment of subclinical hypothyroidism (SCH) with thyrotropin (TSH) < than 10 mU/L are based on the lack of evidence that levothyroxine therapy has beneficial effects. The aim of our study is to estimate the effect of levothyroxine treatment on cardiac morphology and function in subclinical hypothyroidism. Body mass index, waist circumference, blood pressure, electrocardiographic and standard echocardiographic parameters were measured before levothyroxine therapy and 3 months after TSH normalization. Significant reduction in systolic and diastolic blood pressure, PR, QT and QT corrected intervals, as well as increase in heart rate were recorded in the group on levothyroxine therapy. The following parameters of the left and right ventricle were significantly decreased in the treatment group: left ventricular mass index and volume, systolic and diastolic time intervals, and mitral annular plane systolic excursion (MAPSE). The increase was recorded as fractional shortening and pressure rise in early systole (dP/dt), right atrial wall thickness and diameters. Our study did not confirm differences in basic echocardiographic parameters between the treated and control groups, apart from an echocardiographic improvement of cardiac structure and function in treated individuals. The findings suggest electrocardiographic and echocardiographic screening in monitoring the therapeutic effect. https://doi.org/10.2298/ABS191029007P Received: October 29, 2019; Revised: January 5, 2020; Accepted: February 11, 2020; Published online: February 19, 2020 How to cite this article: Pandrc MS, Ristic A, Kostovski V, Milin-Lazovic J, Milic N, Ciric J. The role of echocardiography in monitoring the therapeutic effect of levothyroxine replacement therapy in subclinical hypothyroidism. Arch Biol Sci. 2020;72(1):137-46.