Identifying the optimal atrioventricular (AV) or interventricular (VV) delay is beneficial for patients using cardiac resynchronization therapy (CRT) devices. Ultrasonic echocardiography (UCG) has been the most commonly used method; however, it requires high technical knowledge. Impedance cardiography (ICG) can calculate stroke volume by measuring changes in transthoracic electric impedance. This study sought to assess the clinical utility of ICG in comparison with that of UCG for the optimization of CRT devices. Patients who underwent CRT device implantation were retrospectively analyzed. One week after implantation, optimization of AV delay (AVD) was performed in every patient with ICG (AVD-ICG) and UCG (AVD-UCG). VV delay (VVD) was then determined according to the optimal AVD using these two methods. Forty-two patients were enrolled. Average AVD-ICG was significantly shorter than AVD-UCG (128 ± 49 versus 146 ± 41 milliseconds, P = 0.018). Five patients (12%) had the same optimized AVD with two methods, and the difference between AVD-ICG and AVD-UCG was !20 milliseconds in 19 patients (45%). In the multivariate analysis, the presence of postoperative mitral regurgitation (MR) was an independent predictor of AVD-ICG/AVD-UCG mismatch, defined as a difference over 20 milliseconds (odds ratio = 10.71; 95% confidence interval = 1.72 to 66.72; P = 0.018). The results of optimized VVD were similar using both methods. ICG might be a promising tool for the rapid optimization of CRT devices. However, in patients with moderate-to-severe MR, ICG may not be able to optimize AVD.