Aims Specific septal motion related to dyssynchrony is strongly linked to reverse remodelling, in patients with systolic heart failure (HF) receiving cardiac resynchronization therapy (CRT). We aimed to investigate the relationship between septal deformation patterns studied by longitudinal speckle tracking and clinical outcome following CRT. Methods and results A total of 284 CRT candidates from two centres (HF NYHA classes II-IV, ejection fraction < 35%, QRS >= 120 ms) were prospectively included. Longitudinal strain of the septum in the apical four-chamber view determined three patterns of septal contraction. The endpoints were overall mortality, cardiovascular mortality, and hospitalization for HF. Compared with patterns 1 or 2, pattern 3 was associated with an increased risk for both overall and cardiovascular mortality [hazard ratio (HR) = 3.78, 95% confidence interval (CI): 1.85-7.75, P < 0.001 and HR = 3.84, 95% CI: 1.45-10.16, P = 0.007, respectively] and HF hospitalization (HR = 4.41, 95% CI: 2.18-8.90, P < 0.001). Addition of septal patterns to multivariable models, including baseline QRS width and presence of left bundle branch block, improved risk prediction, and discrimination. In patients with intermediate QRS duration (120150 ms), pattern 3 remained associated with a worse outcome than pattern 1 or 2 (P < 0.05 for all endpoints). Conclusion The identification of septal deformation patterns provides important prognostic information in CRT candidates in addition to ordinary clinical, electrocardiographic, and echocardiographic predictors of outcome in HF patients. This parameter may be particularly useful in patients with intermediate QRS duration in whom the benefit of CRT remains uncertain.