BACKGROUND The His-SYNC pilot trial was the first randomized comparison between His bundle pacing in lieu of a left ventricular lead for cardiac resynchronization therapy (His-CRT) and biventricular pacing (BiV-CRT), but was limited by high rates of crossover. OBJECTIVE To evaluate the results of the His-SYNC pilot trial utilizing treatment-received (TR) and per-protocol (PP) analyses. METHODS The His-SYNC pilot was a multicenter, prospective, single-blinded, randomized, controlled trial comparing His-CRT vs BiV-CRT in patients meeting standard indications for CRT (eg, NYHA II-IV patients with QRS .120 ms). Crossovers were required based on prespecified criteria. The primary endpoints analyzed included improvement in QRS duration, left ventricular ejection fraction (LVEF), and freedom from cardiovascular (CV) hospitalization and mortality. RESULTS Among 41 patients enrolled (aged 64 6 13 years, 38% female, LVEF 28%, QRS 168 6 18 ms), 21 were randomized to His-CRT and 20 to BiV-CRT. Crossover occurred in 48% of His-CRT and 26% of BiV-CRT. The most common reason for crossover from His-CRT was inability to correct QRS owing to nonspecific intraventricular conduction delay (n 5 5). Patients treated with His-CRT demonstrated greater QRS narrowing compared to BiV (125 6 22 ms vs Funding: None. Conflicts of Interest: Dr Gaurav Upadhyay has been a speaker for Abbott, Biotronik and Medtronic, and has been a consultant to Abbott, Biotronik, and Medtronic. Dr Pugazhendhi Vijayaraman has been consultant to Abbott, Biotronik, Boston Scientific, and Medtronic; he also has a patent pending for a His delivery tool. Dr Hemal Nayak has been a speaker for Medtronic, Biotronik, and Boston Scientific. Dr Nishant Verma has been a speaker for Biotronik and Medtronic. Dr Gopi Dandamudi has been a speaker and consultant for Medtronic and serves on the advisory board for Biotronik. Dr Parikshit Sharma has been a speaker for Medtronic and has been a consultant for Abbott and Biotronik. Dr Moeen Saleem has been a speaker for Abbott, Medtronic, and Boston Scientific. Dr Faiz Subzposh has been a consultant to Medtronic. Dr Zaid Aziz has been a speaker for Biotronik. Dr Richard Trohman has been a speaker for Abbott, AltaThera Pharmaceuticals, Boston Scientific, Daiichi Sankyo, and Medtronic; he has been an advisor to Boston Scientific; he has received research grants from