BackgroundHis-Purkinje system pacing (HPSP), including his-bundle pacing (HBP) and left bundle branch area pacing (LBBaP), imitates the natural conduction of the heart as an alternative to biventricular pacing (BVP) in cardiac resynchronization therapy (CRT). However, the feasibility and efficacy of HPSP were currently only evidenced by studies with a limited sample size, so this study aimed to provide a comprehensive assessment through a systematic review and meta-analysis.MethodsIn order to compare the clinical outcomes associated with HPSP and BVP in patients for CRT, PubMed, EMBASE, Cochrane Library and Web of Science database were searched from inception to April 10, 2023. Clinical outcomes of interest including QRS duration (QRSd), left ventricular (LV) function and New York Heart Association (NYHA) functional classification, pacing threshold, echocardiographic and clinical response, hospitalization rate of HF and all-cause mortality were also extracted and summarized for meta-analysis.ResultsA total of 13 studies (ten observational studies and three randomized studies) involving 1,121 patients were finally included. The patients were followed up for 6–27 months. Compared with BVP, CRT patients treated by HPSP presented shorter QRSd [mean difference (MD): -26.23 ms, 95% confidence interval (CI): -34.54 to -17.92,P< 0.001,I2= 91%], greater LV functional improvement with increased left ventricular ejection fraction (LVEF) (MD: 6.01, 95% CI: 4.81 to 7.22,P< 0.001,I2= 0%), decreased left ventricular end-diastolic dimension (LVEDD) (MD: -2.91, 95% CI: -4.86 to -0.95,P= 0.004,I2= 35%), and more improved NYHA functional classification (MD: -0.45, 95% CI: -0.67 to -0.23,P< 0.001,I2= 70%). In addition, HPSP was more likely to have higher echocardiographic [odds ratio (OR): 2.76, 95% CI: 1.74 to 4.39,P< 0.001,I2= 0%], clinical (OR: 2.10, 95% CI: 1.16 to 3.80,P= 0.01,I2= 0%) and super clinical (OR: 3.17, 95% CI: 2.09 to 4.79,P< 0.001,I2= 0%) responses than BVP, and a lower hospitalization rate of HF (OR: 0.34, 95% CI: 0.22 to 0.51,P< 0.001,I2= 0%), while presented no difference (OR: 0.68, 95% CI: 0.44 to 1.06,P= 0.09,I2= 0%) in all-cause mortality compared with BVP. With threshold change taking into account, BVP was less stable than LBBaP (MD: -0.12 V, 95% CI: -0.22 to -0.03,P= 0.01,I2= 57%), but had no difference with HBP (MD: 0.11 V, 95% CI: -0.09 to 0.31,P= 0.28,I2= 0%).ConclusionThe present findings suggested that HPSP was associated with greater improvement of cardiac function in patients with indication for CRT and was a potential alternative to BVP to achieve physiological pacing through native his-purkinje system.Graphical AbstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s12872-023-03307-7.