Cardiac resynchronization therapy (CRT) is a standard treatment for selected patients with chronic heart failure (HF). However, up to 30-50% of patients still do not respond to CRT.Our aim was to identify the predictive value of S wave in lead V6 on CRT response in patients with complete left bundle branch block (CLBBB).The CLBBB definition included the Strauss LBBB criteria and the absence of q waves in leads I, V5 and V6. According to electrocardiogram (ECG) at baseline, CLBBB patients were divided into 3 groups: T-CLBBB group (CLBBB without S wave in V5 or V6), V5S group (CLBBB with S wave in V5 and no S wave in V6) and V5&V6S group (CLBBB with S wave in V5 and V6). CRT response was defined as left ventricular end-systolic volume (LVESV) reduction ≥ 15% at 6-month follow-up. The combined endpoint included HF rehospitalization or all-cause death.Of 181 LBBB-like pattern patients, 112 CLBBB patients were included into 3 groups: 54 in T-CLBBB, 32 in V5S and 26 in V5&V6S group. CRT response rate was 85.2%, 65.6% and 38.5% respectively (p<0.001). Kaplan-Meier curves demonstrated that patients in V5&V6S group had higher incidence of HF rehospitalization or all-cause death than that in the other two groups (P<0.001). In a multivariate logistic regression model analysis, S wave in lead V6 was significantly associated with CRT non-response (HR: 0.33; 95% CI:0.11-0.96; P=0.042).S wave in lead V6 can predict low response to CRT and poor long-term outcome.