Risk of infection is an important consideration for patients undergoing cardiac implantable electronic device (CIED) procedures. We examined the comparative incidence and associations of device infection for patients undergoing either de novo CIED implant or device re-intervention. Data were extracted from a high-volume UK centre from 2016-2019. Patient demographics, procedural parameters and outcomes were examined according to two groups: ‘De novo implants’ (all transvenous CIED implants) and ‘Re-interventions’ (generator replacement or revision, new lead insertion without extraction, and lead extraction). Patients undergoing re-intervention for device infection were excluded. During follow-up, a device infection was defined as a clinical diagnosis of pocket or systemic infection requiring intervention within 90 days of the index procedure. 7,384 procedures were included. There were 4,837 de novo implants (61.2% dual chamber, 22.5% single chamber, 16.1% biventricular devices) and 2,547 re-interventions (53.4% generator replacement, 27.9% new lead, 16.6% lead extraction). All patients received a pre-procedural bolus of two intravenous antibiotics. 43 device infections were recorded (0.58%). There was an exponential relationship between intervention number and infection incidence; de novo implant: 0.27%, 2nd intervention: 1.01%, 3rd (or greater) intervention: 3.3%. Adjusting for indication, type of re-intervention performed, device type, and patient co-morbidities (Age, Sex, LV function, ischaemic heart disease, cardiomyopathy, atrial fibrillation), intervention number was an independent predictor of device infection versus de novo implant (adjusted OR 4.6 (2.1-10), p<0.0001). The risk of infection from device re-intervention was significant, cumulative, and occurred independently of procedure type and patient parameters. This data should contribute to procedural decision-making, particularly for patients in whom the indication for re-intervention may be equivocal.