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Aim: Cardiac resynchronization therapy (CRT) is a cornerstone in the management of chronic heart failure in patients with a broad or paced QRS. However, data on long-term outcome after upgrade to CRT are scarce., Methods and Results: This international, multicentre retrospective registry included 2275 patients who underwent a de novo or upgrade CRT implantation with a mean follow-up of 3.6 ± 2.7 years. The primary composite endpoint included all-cause mortality, heart transplantation, or ventricular assist device implantation. The secondary endpoint was first heart failure admission. Multivariable Cox regression and propensity score matching (PSM) analyses were performed. Patients who underwent CRT upgrade (n = 605, 26.6%) were less likely female (19.7% vs. 28.8%, p < 0.001), more often had ischeemic cardiomyopathy (49.8% vs. 40.2%, p < 0.001), and had worse renal function (median estimated glomerular filtration rate 50.3 ml/min/1.73 m 2 [35.8-69.5] vs. 59.9 ml/min/1.73 m 2 [43.0-76.5], p < 0.001). The incidence rate of the composite endpoint was 10.8%/year after CRT upgrade versus 7.1%/year for de novo implantations (p < 0.001). PSM for the primary endpoint resulted in 488 pairs. After propensity score matching, upgrade to CRT was associated with a higher chance to reach the composite endpoint (multivariable hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.08-1.70), for both upgrade from pacemaker (multivariable HR 1.33, 95% CI 1.03-1.70) and implantable cardioverter-defibrillator (ICD) (multivariable HR 1.40, 95% CI 1.01-1.95). PSM for the secondary endpoint resulted in 277 pairs. After PSM, upgrade to CRT was associated with a higher chance for heart failure admission (HR 1.74, 95% CI 1.26-2.41)., Conclusion: In this retrospective analysis, the outcome of patients who underwent upgrades to CRT differed significantly from patients who underwent de novo CRT implantation, particularly for upgrades from ICD. Importantly, this difference in outcome does not imply a causal relation between therapy and outcome but rather a difference between two different patient populations., (© 2023 European Society of Cardiology.)