Introduction <p>Left bundle branch area pacing (LBBAP) includes both left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP). Although frequently considered equivalent, data regarding clinical outcomes with each of these pacing strategies in patients requiring cardiac resynchronization therapy (CRT) is limited.</p> Methods <p>Studies comparing LBBP and LVSP for CRT in patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) were included. The primary outcomes were HF-related hospitalization and all-cause mortality. Secondary outcomes included procedural times, paced QRS duration, procedure-related complications, and change in LVEF.</p> Results <p>Four studies involving 384 patients (pooled weighted mean age 68.28 ± 11.04 years; pooled weighted mean LVEF of 31.1 ± 7.3%) were included. Compared to LVSP, LBBP was associated with a significant reduction in the risk of HF-related hospitalization (HR 0.27; 95% CI 0.11–0.7; p&lt;0.001, I²=49%) without a significant difference in all-cause mortality (HR 0.34; 95% CI 0.07-1.53; p=0.16; I²=69%). There was also a significant improvement in LVEF (mean weighted difference: 4.46%; 95% CI: 0.4–8.52; p= 0.03; I² = 46) as well as shorter paced QRS duration (pooled weighted mean QRS duration 124.1 ±19.9 ms vs. 142.8 ± 23.3 ms; mean weighted difference: -16.78 ms, 95% CI -27.42 to -6.15 ms, p 0.002, I2 80%). LBBP was not associated with longer procedural duration compared with LVSP.</p> Conclusion <p>In patients undergoing LBBAP for CRT, LBBP is associated with significant reductions in HF-related hospitalization, as well as significant improvements in LVEF and shorter paced QRS durations. Given our results, LVSP should not be considered equivalent to LBBP, and all efforts should be made to capture the cardiac conduction system in patients undergoing LBBAP CRT.</p> Graphical Abstract <p></p>