Abstract Background Staphylococcus aureus bacteraemia (SAB) is a serious condition with high morbidity and mortality. Patients with a cardiac implantable electronic device (CIED) and SAB carries a risk of up to 50 % for device related infection. Yet, little is known about risk factors for early and late SAB in CIED patients in real-world clinical practice. Purpose We aimed to identify risk factors associated with first-time early and late SAB following de novo CIED implantation among adult Danish patients. Methods Using the Danish Pacemaker and ICD Register, we identified all Danish patients aged 18 to 99 years with a first CIED implantation between 2000 and 2020. The primary outcome of first-time post-CIED implantation SAB was identified from The National Danish Staphylococcus Aureus Bacteriemia Database. Early SAB was defined as SAB ≤ 6 months from CIED implantation. Late SAB was defined as first-time SAB after CIED, occurring > 6 months from CIED implantation. Multivariable Cox regression with backward elimination was used to identify factors associated with increased risk of developing early and late SAB. Age, sex, device type, implantation year, preexisting co-morbidity, procedure related factors and prior surgery (thoracic, abdominal, orthopedic, gynecologic, or urologic) was evaluated. Statistically significant variables were fitted to the final models to obtain hazard ratios with 95% confidence intervals. Results We identified 87,216 patients with first-time CIED implantation within the study period: PM n = 66,151 (75.8%); Implantable Cardioverter Defibrillator (ICD) n = 13,498 (15.5%); Cardiac resynchronization therapy PM (CRT-P) n = 3,491 (4.0 %); Cardiac resynchronization therapy with defibrillator (CRT-D) n = 4,076 (4.7 %). Median age across the population was 75 years (IQR 66-82) and 62.6% were males. Median time to SAB in the early SAB group was 46 days (IQR 18-105) and 2,9 years (IQR 1.5-5.1) in the late SAB group. Post implantation SAB was observed in 1,399 (1.6%) patients; with 363 (25.9%) early SAB events and 1,036 (74.1%) late SAB events. Factors associated with early SAB included previous SAB, renal dialysis, COPD, surgery 1 year prior to CIED implantation, liver disease, diabetes, and congestive heart failure (Figure 1). Male sex, increasing age, previous SAB, congestive heart failure, aortic valve disease, diabetes, renal dialysis, COPD, cancer, liver disease and the use of systemic corticosteroids were associated with an increased risk of late SAB. Conclusions Renal dialysis, previous SAB, diabetes, congestive heart failure, COPD and liver disease were associated with an increased risk of both early and late SAB. Increasing age, male sex, aortic valve disease and cancer were associated with an increased risk of late SAB, while surgery within 1 year prior to CIED implantation was associated with early SAB. Most of the identified factors were non-modifiable and comparable to known risk factors for SAB in non-CIED patients.Figure 1