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Background: Cardiac device-related infective endocarditis (CDRIE) is one of the most serious complications of cardiac resynchronisation therapy (CRT)., Aim: We sought to assess clinical outcomes and their determinants in CRT patients with CDRIE., Methods: A tertiary cardiology centre database was screened to identify all CDRIE cases, diagnosed based on the modified Duke criteria, amongst 765 consecutive CRT implantations performed between 2002 and 2015 (70.8% de novo implantations, 29.2% upgrades)., Results: During the median follow-up of 1692 days (range: 457-3067 days) CDRIE was diagnosed in 41 (5.4%) patients. Overall, in-hospital and long-term mortality rates of CDRIE patients were 51.2% and 75.6%, respectively. Among patients with CDRIE, in whom the device was vs. was not explanted, in-hospital death rates were 39.3% (11/28 patients) vs. 76.9% (10/13 patients; p = 0.025). In multivariate regression analysis, device removal was independently associated with significantly lower in-hospital mortality (hazard ratio [HR] 0.09, 95% confidence interval [CI] 0.03-0.35, p = 0.0004). The need for temporary pacing after device removal (HR 5.92, 95% CI 1.13-30.96, p = 0.035), a time period of less than seven days between CDRIE diagnosis and CRT removal (HR 6.69, 95% CI 1.48-30.27, p = 0.01), and the highest serum creatinine level during infection (HR 1.02, 95% CI 1.004-1.03, p = 0.01) were identified as independent predictors of higher in-hospital mortality., Conclusions: Device removal is independently associated with lower mortality in patients with CRT and CDRIE. Early device removal (less than seven days since the diagnosis), the need for temporary pacing after removal and acute renal failure are independent mortality predictors in CRT patients who developed CDRIE.