Abstract Background According to current guidelines, complete removal of cardiac implantable electronic device (CIED) should be considered in patients with valvular infective endocarditis (IE), accounting for the identified pathogen and need for valve surgery (Class IIa recommendation). Unselected longitudinal data are needed to assess this strategy. Purpose To examine IE readmission after IE discharge according to status of CIED removal in patients with conservatively treated IE. Methods Using Danish nationwide registries, we identified patients aged ≥18 years with first-time IE from 2010-2021. We included patients with conservatively treated IE and a CIED, who were alive at IE discharge. Patients who underwent CIED removal during IE admission were compared to those without removal, examining the study outcome of IE readmission within six months after IE discharge. An initial blanking period of 14 days was applied after IE discharge. The Aalen-Johanson estimator and multivariable Cox regression models were used to determine cumulative incidences and adjusted hazard ratios (HRs) of IE readmission according to status of CIED removal, respectively. Results Among 6,843 patients with first-time IE, 5,731 (83.7%) were conservatively treated. Of these, 1,201 (21.0%) had a CIED, of which 205 (17.1%) died during IE admission. Thus, the final study population comprised 996 patients alive at IE discharge. The median age of the study population was 75.5 years (interquartile range [IQR]: 67.9-82.0), and 753 (75.6%) were males. In total, 574 (57.6%) patients underwent CIED removal during IE admission. Patients who underwent CIED removal were younger, compared to patients without CIED removal, 73.1 years (IQR: 65.7-79.1) versus 79.0 years (IQR: 71.3-85.1), respectively. The six-month cumulative incidence of IE readmission was 2.0% (95% confidence interval [CI]: 1.1-3.5%) in patients who underwent CIED removal versus 6.1% (95% CI: 4.0-8.9%) in patients without CIED removal (P-value=0.001) (Figure 1). CIED removal was associated with a significantly lower six-month rate of IE readmission, compared to no CIED removal (HR: 0.36 [95% CI: 0.17-0.77]). Relapse bacteraemia (including IE) with the same microorganism as first-time IE occurred in 2.2% of patients who underwent CIED removal and in 5.4% of patients without CIED removal. Staphylococcus aureus was the most common microorganism in 33.3% of patients with relapse bacteraemia who underwent CIED removal. Conclusions In this nationwide study, the six-month rate of infective endocarditis (IE) readmission was three-fold lower in patients who underwent cardiac implantable electronic device (CIED) removal, compared to patients without CIED removal. The current findings suggest that CIED removal is associated with lower risk of relapse of IE in patients with conservatively treated IE. These results are in line with current guideline recommendations. However, more randomized clinical trial data are needed.