BackgroundLeft bundle branch area pacing (LBBaP) has recently emerged as alternative a new physiologic strategy of pacing to His-bundle pacing (HBP) associated with difficulty of lead implantation, His bundle damage, high and unstable thresholds.ObjectiveThe purpose of this study is to compare clinical safety and efficacy of LBBaP with right ventricular sepal pacing (RVSP).MethodsFrom February 2019 to May 2020, consecutive pacing-indicated patients were prospectively enrolled and divided into two groups. Ventricular synchrony index such as QRS duration (QRSd), interventricular mechanical delay (IVMD) and septal-posterior wall motion delay (SPWMD), left ventricular function such as left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF), pacing parameters, and complications were evaluated in perioperative period and during follow-up.ResultsLBBaP was successful in 45 patients (88.2%), and finally 46 patients underwent RVSP. With LBBaP, the ventricular electrical- mechanical synchrony were similar with the native-conduction system (P = .784). However, the ventricular electrical synchrony (QRSd, 108.47 ± 7.64 vs 130.63 ± 13.63 ms, P < .0001) and mechanical synchrony (IVMD, 27.68 ± 4.33 vs 39.88 ± 5.83, P < .0001; SPWMD, 40.39 ± 23.21 vs 96.36 ± 11.55, P < .0001) in the LBBaP group were significantly superior to the RVSP group. No significant differences in LVEDD (46 [44-48.5] vs 47 [44–52] mm, P = .488) and LVEF% (66 [62.5–70] vs 64 [61–68], P = .759) were noted in both two groups at last follow-up. But, in the subgroup analysis, LVEDD was shorter (46 [44–49] vs 50 [47–58] mm, P = .032) and the LVEF% was higher (65 [62–68] vs 63 [58–65], P = .022) in the LBBaP-H (high ventricular pacing ratio > 40%) group compared with RVSP-H group at last follow-up. There was lower capture thresholds (0.59 ± 0.18V vs. 0.71 ± 0.26V, P = 0.011) at implantation in the LBBaP group than RVSP group, and R-wave amplitudes and pacing impedances did not differ between the two groups. No serious complications were found in both two groups at implantation and follow-ups.ConclusionThis study confirms the clinical safety and efficacy of LBBaP, and that produces better ventricular electrical-mechanical synchrony than RVSP. The event of pacing-induced left ventricular dysfunction is lower in the LBBaP-H group than RVSP-H group.Trial registrationTrial registration Chinese Clinical Trial Registry, ChiCTR2100046901, Registered 30 May 2021—Retrospectively registered, http://www.chictr.org.cn/searchproj.aspx?regstatus=1008001.