Objectives Septal wall motion abnormalities are frequently observed in patients with left bundle branch block (LBBB). However, septal wall thickening in LBBB patients has not been thoroughly evaluated. Methods and results To investigate the relationship between septal wall motion and wall thickening, we studied 31 normal control subjects, 24 LBBB patients with normal wall motion (LBBB-NWM), and 24 LBBB patients with septal dyssynchrony (LBBB-SDS), all with a low likelihood (<15%) of coronary artery disease. The septal and lateral quadrants of the left ventricle were analyzed in stress 8-frame gated technetium 99m sestamibi tomograms. The percent wall thickening was calculated by use of a 25-segment polar map with the p-FAST software program by two independent methods: the regional count density increase from end diastole to end systole (CD method) and the geometric increase in the distance between the 50% thresholded endocardial and epicardial borders from end diastole to end systole (GD method). In addition, the ratio of septal/lateral percent wall thickening was calculated. The relative septal wall thickening in the entire LBBB population was decreased as compared with the normal control subjects (0.35 ± 0.37 vs 0.81 ± 0.17, P < .001). Decreased wall thickening was observed in not only LBBB-SDS patients but also to a lesser degree in LBBB-NWM patients (0.12 ± 0.35, P < .001; 0.57 ± 0.24, P = .005, respectively). This abnormality was most apparent when the CD method was used. Conclusions Septal wall thickening is decreased in patients with LBBB even with normal wall motion. LBBB per se may compromise septal wall thickening, and dyssynchronous wall motion results in further deterioration of wall thickening.