Introduction: Cardiac resynchronization therapy (CRT) through biventricular pacing (BVP) is the standard treatment for heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB). Left bundle-branch area pacing (LBBAP) has emerged as a potentially more effective approach. However, its superiority over BVP remains unclear. Hypothesis: Is LBBAP more effective and safer than BVP for CRT in patients with HFrEF? Methods: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) or observational studies that reported adjusted effect estimates (i.e propensity score-matched populations or multivariate analysis), comparing the efficacy and safety of LBBAP versus BVP. We applied the random-effects model to calculate adjusted hazard ratio (aHR) and mean difference (aMD), with the corresponding 95% confidence interval. Heterogeneity was assessed using I 2 statistics. Statistical analysis was performed using R version 4.2.1. Results: Our analysis included 7 studies, yielding 2,743 patients, of whom 1,164 (42.4%) were assigned to LBBAP group. Compared with BVP, LBBAP was associated with a significant reduction of the composite of overall mortality and heart failure hospitalizations (aHR 0.67; 95% CI 0.56-0.80; I 2 =0%; p<0.001; Figure 1A). Additionally, LBBAP demonstrated a significant increase in LVEF (aMD 5.77%; 95% CI 2.94-8.60; I 2 =68%; p<0.001; Figure 1B) and shortening of QRS duration (aMD -25.71 ms; 95% CI -35.87 to -15.55; I 2 =0%; p<0.001; Figure 2A) compared with BVP. Sub-analysis of patients with LBBB also demonstrated a significant reduction of the composite of overall mortality and heart failure hospitalizations (aHR 0.64; 95% CI 0.49 to 0.85; I 2 =0%; p<0.001; Figure 2B) in LBBAP. Conclusions: This meta-analysis of RCTs and multivariable adjusted studies suggests that LBBAP is superior to BVP in patients with HFrEF undergoing CRT for both electrophysiological and clinical outcomes.