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Background Current guidelines recommend complete removal of a cardiac implantable electronic device (CIED) in patients with infective endocarditis (IE), although these recommendations are largely based on expert opinion (level of evidence C). We aimed to examine outcomes stratified by CIED removal status in patients with IE.Methods Using Danish nationwide registries (2010–2021), we identified patients aged ≥18 years with first-time IE, who were alive at discharge, managed without valve surgery and had a CIED. Patients who underwent CIED removal during IE admission were compared with those without removal. The study outcomes were IE readmission, recurrent bacteraemia (including IE with the same microbial aetiology) and all-cause mortality within 6 months after discharge.Results The study population comprised 1040 patients with non-surgically managed IE and a CIED, and among these, 596 (57.3%) underwent CIED removal during admission. Patients who underwent removal were younger and less frail than those without removal. In the removal versus non-removal group, the 6-month cumulative incidences were 2.5% (95% CI 1.4% to 4.1%) vs 7.1% (95% CI 4.9% to 9.9%) for IE readmission (p value <0.001), 2.1% (95% CI 1.1% to 3.5%) vs 5.2% (95% CI 3.4% to 7.6%) for recurrent bacteraemia (p value=0.005) and 11.5% (95% CI 9.1% to 14.3%) vs 20.0% (95% CI 16.4% to 23.9%) for all-cause mortality (p value <0.001). In multivariable Cox regression models, CIED removal was associated with lower 6-month rates of IE readmission (HR 0.39 (95% CI 0.19 to 0.79)) and all-cause mortality (HR 0.70 (95% CI 0.49 to 0.996)), compared with no removal.Conclusions In this nationwide study of patients with non-surgically managed IE and a CIED, CIED removal was associated with significantly lower 6-month rates of IE readmission, recurrent bacteraemia and mortality compared with no removal, supporting current guideline recommendations. However, randomised clinical trials are warranted to determine the most effective treatment strategy.