Introduction: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing, MPP) has been shown to improve CRT response, although MPP response using automated pacing vector programming has not been demonstrated in the Middle East. Objective: Compare the impact of MPP to conventional biventricular pacing (BiV) using echocardiographic and clinical changes at 6 months post-implant. Methods: This prospective, randomized study was conducted at 13 Middle Eastern centers. After de novo CRT-D implant (Abbott Unify Quadra MP™ or Quadra Assura MP™) with quadripolar LV lead (Abbott Quartet™), patients were randomized to either BiV or MPP therapy. In BiV patients, the LV pacing vector was selected per standard practice; in MPP patients, the two LV pacing vectors were selected automatically using VectSelect. CRT response was defined at 6 months post-implant by a reduction in LV end-systolic volume (ESV) ≥15%. Results: One-hundred and forty-two patients (61 years old, 68% male, NYHA class II/III/IV 19%/75%/6%, 33% ischemic, 57% hypertension, 52% diabetes, 158 ms QRS, 25.8% ejection fraction [EF]) were randomized to either BiV (N=69) or MPP (N=73). After 6 months, MPP vs. BiV patients experienced greater ESV reduction (25.0% vs. 15.3%, P=0.08), greater EF elevation (11.9% vs. 8.6%, P=0.36), significantly greater ESV response rate (68.5% vs. 50.7%, P=0.04), and significantly greater NYHA class improvement rate (80.8% vs. 60.3%, P=0.01). Conclusions: With MPP and automatic LV vector selection, more CRT patients in the Middle East experienced reverse remodeling and clinical improvement relative to conventional BiV pacing.