Abstract Background Permanent His bundle pacing (HBP) is a more physiological technique for cardiac stimulation and has recently emerged as an alternative for anti-bradycardia pacing and cardiac resynchronization therapy (CRT). Its main advantages over “classical” pacing are both its protective role over pacing-induced cardiomyopathy and the possibility of resynchronization by normalization of His-Purkinje activation. Objective To evaluate the intermediate-term outcomes of HBP in terms of safety, performance, and clinical outcomes. Methods Between December 2018 and July 2020, we enrolled a series of consecutive patients with indication for pacing in whom HBP was attempted. A specific lead (3830 Select Secure MRI SureScan) and sheath (C315His) were used. At follow-up clinical, safety and performance outcomes were evaluated. A significant rise in HBP pacing threshold was defined as an increase of at least 1V@1msec in the minimum voltage that could produce an effective myocardial depolarization. Remote or in-hospital device interrogation was performed by an experienced electrophysiologist. Results HBP was attempted in 99 patients and all implantations were performed by the same two operators. 82 procedures were successful (83%). The main reasons for HBP failure were high pacing-thresholds (n=8, 47%), infra-hisian block (n=5, 29,4%), difficult HB location (n=3, 17,6%), unsatisfactory sensing (n=1, 5,9%) or lead instability (n=1, 5,9%). During a mean follow up of 9,5±5.9 months, the overall technical and clinical complication rates were 39% and 13,3% respectively. 3 (3.6%) patients underwent His lead extraction and subsequent conventional right ventricular septum (RV) lead implantation because of lead dislodgement (n=2) or rise in pacing threshold (n=1), while 2 (2.4%) patients required His lead repositioning because of lead dislodgement (n=1) and phrenic nerve stimulation (n=1). 19 patients (23,2%) experienced a significant rise in Hisian pacing threshold and 1 of these patients also had poor sensing parameters. Oversensing was noted in 8 (9.7%) patients and in 7 of them (87.5%) it was due to both atrioventricular and ventriculoatrial crosstalk events. As regards clinical outcomes, 7 patients (8.5%) were diagnosed with new onset atrial fibrillation (AF), one of them complicated by stroke. 3 patients (3.6%) were hospitalized for acute heart failure, 1 of them after His lead dislodgement. Finally, 5 patients (6.1%) died during follow-up, but no death was related to cardiovascular events. Conclusions HBP is an effective technique to obtain a more physiological cardiac pacing but it is limited by a moderate rate of procedural failure and follow-up complications, mainly rising in pacing threshold and oversensing events. This is probably due to suboptimal implantation tools and lack of specific programming algorithms. New dedicated tools, increased experience and knowledge of device limitations and optimal programming are needed to improve future outcomes. Funding Acknowledgement Type of funding sources: None.