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Background: Cardiac resynchronization therapy is a guideline-recommended therapy in patients with heart failure, mildly reduced left ventricular ejection fraction (HFmrEF 36-50%), and left bundle branch block or indication for ventricular pacing. Conduction system pacing (CSP) utilizing left bundle branch area pacing (LBBAP) or His bundle pacing (HBP) has been shown to be a safe and physiologic alternative to biventricular pacing (BVP)., Objective: The aim of this study was to compare the clinical outcomes between BVP and CSP among patients with HFmrEF undergoing CRT., Methods: Consecutive patients who underwent BVP or CSP in patients with HFmrEF between Jan 2018 to June 2023 at 16 international centers were included. The primary outcome was the composite endpoint of time to death or HFH. Secondary endpoints included change in LVEF and individual endpoints of death and HFH., Results: A total of 1004 patients met inclusion criteria: BVP 178, CSP 826 (HBP 154; LBBAP 672). Mean age was 73±13 yrs, female 34%, and LVEF 42±5%. Paced QRS duration in CSP was significantly narrower compared to BVP (129±21 vs 144±19, p<0.001). LVEF improved during follow-up in both groups (49±10 vs 48±10%, p=0.32). CSP was independently associated with significant reduction in the primary endpoint of time to death or HFH compared to BVP (22% vs 34%; HR 0.64; 95% CI 0.43-0.94; p=0.025)., Conclusions: CSP was associated with improved clinical outcomes when compared to BVP in this large cohort of patients with HFmrEF undergoing CRT. Randomized controlled trials comparing CSP to BVP will be necessary to confirm these results., (Copyright © 2024. Published by Elsevier Inc.)