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Background Staphylococcus aureus infective endocarditis (SA-IE) remains a serious condition, with in-hospital mortality rates ranging between 30% and 40%. While current guidelines suggest surgery may be considered in all SA-IE cases, robust data comparing outcomes between patients undergoing surgery and those receiving medical therapy alone are scarce.Methods Using the NatIonal Danish endocarditis stUdieS registry, we identified all patients with left-sided SA-IE between 2016 and 2021. Patients were categorised into two groups: surgical and non-surgical. Baseline characteristics were assessed, and in-hospital mortality was analysed using crude estimates and multivariable Cox regression.Results Of 918 patients identified, 160 (17%) patients underwent surgery (median age 63.7 years; 73% male), and 758 (83%) were treated non-surgically (median age 75.0 years; 58% male). Surgical patients had fewer comorbidities, including diabetes (18% vs 27%) and congestive heart failure (6% vs 19%). Surgical patients presented at admission with more severe conditions, including larger vegetations (56% vs 21%), sepsis (53% vs 33%) and emboli (24% vs 10%). Crude in-hospital mortality was lower in the surgical group (17% vs 28%), as was 1 year mortality (21% vs 45%). After adjusting for confounders, there was no significant difference in adjusted in-hospital mortality between the groups (HR 0.75 (95% CI 0.47 to 1.19)); however, 1-year mortality was statistically significantly lower in surgical patients (HR 0.61 (95% CI 0.41 to 0.91)).Conclusion In patients with SA-IE, surgical patients were younger and had fewer comorbidities, but had more severe disease status at admission, compared with non-surgical patients. Surgery was associated with lower 1-year mortality, but the heterogeneity of this patient population limits firm conclusions about the superiority of either treatment strategy.