Abstract Background The incidence of infective endocarditis (IE) is increasing in the adult population, as is the insertion of prosthetic heart valves. Patients with prosthetic heart valves are considered at high risk of IE – a complication with a high mortality. However, data on temporal changes in the incidence of IE among patients with prosthetic heart valves from unselected cohorts are sparse Purpose We aimed to examine nationwide temporal trends in the incidence of IE in patients with an implanted prosthetic heart valve in Denmark from 1999 to 2018. Methods Using Danish nationwide health-care registries we identified all patients, who underwent heart valve implantation between 1996–2018. Crude annual incidence rates per 1,000 person years (PY) of IE were computed and presented in two year intervals. Analyses were stratified by sex and age groups (<50, 50–59, 60–69, 70–79, >80 years). Results We identified 26,604 patients with first time prosthetic valve implantation with a median age of 72.7 years at the time of implantation, 63.1% were men with a median follow-up of 6.5 years. We found 1,442 cases of first time IE. The IE incidence rate ranged from 5.4 /1,000 PY (95% CI 3.9–7.4) in calendar period 2001–2002 to 10.0/1,000 PY (95% 8.84–11.11) in calendar period 2017–2018 with an unadjusted increasing trend during the study period (ptrend<0.0001), (Figure 1). Overall, men had a higher crude incidence rate compared with women, however no significant temporal changes were seen in the incidence rate during the study period. For age groups, a trend of stepwise increase in the incidence rate of IE was observed for increasing age groups, however no temporal changes were observed (Figure 2). Conclusion The incidence of IE following prosthetic heart valve implantation has increased slightly over the last 20 years in Denmark. Funding Acknowledgement Type of funding sources: None.