Abstract Background Surgery is often indicated in patients with infective endocarditis (IE), but the survival benefits of surgical intervention have not been validated in large-scale studies. Although previous studies appeared to support early surgical intervention, the optimal timing of intervention remains uncertain. Purpose We aim to evaluate the benefits of surgery and identify the optimal timing of surgical intervention for patients with IE. Methods From a well-validated territory-wide database in Hong Kong, all patients aged 20 or above diagnosed with incident IE from 2000–2019 were included. Patients were divided into those who received surgical intervention within 1 year of IE (surgical cohort) and those who did not (control cohort). The two cohorts were then compared using inverse probability weighting of the covariate balancing propensity score, which included demographics, comorbidities, and causative organism as covariates. Outcomes of interest include, at 1 year, all-cause death, and the development of complications. A Cox proportional hazards model was used to evaluate the association between surgical intervention and death, with “doubly-robust estimation” used to minimise the effect of confounders. For complications, a Fine-Gray model was used to account for competing risk. The surgical cohort was subdivided into early (≤7 days of hospitalisation) or late surgical intervention; a similar propensity score analytic approach was used to evaluate the effects of early vs. late intervention, with those who died within the 7 days excluded to ensure a fair comparison. Results A total of 5,657 patients (age 59.9±18.3 years, 37.2% females) were included, of which 930 (16.4%) received surgical intervention in 1 year. Overall, the surgical cohort had a 45% risk reduction in all-cause death (hazard ratio [HR] 0.55, 95% CI [0.46 to 0.65], P<0.001) (Figure). This association remained consistent in subgroup analysis stratified by age, sex, and causative organisms (Table 1). The surgical cohort also had a lower risk of complications, including acute kidney injury (HR 0.61, 95% CI 0.43 to 0.87, P=0.006), systemic embolism (HR 0.35 [0.23 to 0.55], P<0.001), ischaemic stroke (HR 0.37 [0.24 to 0.55], P<0.001), cardiac dysrhythmia (HR 0.79 [0.66 to 0.95], P=0.011), and pneumonia (HR 0.36 [0.26 to 0.49], P<0.001). In the surgical cohort, compared to those who had early surgery (N=181), those with delayed surgery had a lower risk of all-cause death (HR 0.58 [0.34 to 0.99], P=0.045) (Figure) and complications (Table 2) at 1 year. In those who had early surgery, patients who received ultra-early surgery (≤3 days of hospitalisation, N=104) did not have a significantly different risk of death (HR 1.19 [0.47 to 3.34], P=0.654). Conclusions Surgical intervention significantly reduced the risk of death and complications in patients with infective endocarditis. Delayed surgical intervention appeared to be more protective. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Shenzhen Key Medical DisciplineThe Sanming Project of HKU-SZH Cardiology