Introduction Optimization of cardiac resynchronization therapy (CRT) using a 12-lead electrocardiogram (ECG) alone may not sufficiently improve left ventricular (LV) function in all cases. Therefore, we aimed to investigate whether additional optimization using transthoracic echocardiography (TTE) could further enhance CRT efficacy. Methods Sixty-five patients who underwent CRT implantation between March 2018 and July 2022 at Sakakibara Heart Institute, Japan, were included in this study. Data were collected at three points: before optimization (point A), after ECG-based optimization (point B), and after TTE-based adjustments (point C). Results The mean age was 74±11 years (male: 78.4%). The PR interval was significantly prolonged at points B and C compared with that at point A. The QRS width narrowed significantly at point B (119±20 ms vs. 137±20 ms, p<
0.01) but increased at point C (124±20 ms), approaching point A levels. Thirty-six patients achieved LV dyssynchrony improvement with ECG optimization alone, whereas 29 required TTE adjustments for further improvement. Patients needing TTE optimization had higher QRS width at point C than at point B. TTE adjustments significantly improved LV ejection fraction (28.1±6.8% to 31.5±8.0%, p=0.01) and reduced septal flash (46.2% to 15.4%, p=0.04). The need for TTE adjustments was similar to the usage of CRT devices with and without auto-adjustment functions. Conclusion TTE-based optimization enhances LV function and synchrony in cases where ECG-based adjustments alone are insufficient, highlighting the importance of TTE evaluation in CRT optimization.