Introduction: Splenic abscess is a rare and highly morbid extracardiac manifestation of infective endocarditis (IE) and has only been described in small case series in the literature. Emergency surgeons are often consulted for splenectomy; however, the optimal timing (before or after valve) of this intervention remains unclear. We hypothesized that definitive valve intervention, prior to splenectomy, would lead to superior patient outcomes. Study design: A retrospective review of patients with IE and splenic abscess from June 2011 to June 2016 was performed at a quaternary referral center in the United States. Demographics, comorbid conditions, echocardiography results, intensive care unit (ICU)/hospital length of stay, operative interventions, splenectomy and valve replacement, and complications were collected. Patients were divided based on operation performed first: spleen first (SF) or valve first (VF). The primary outcome was mortality, with secondary outcomes including in-hospital morbidity. Results: Ten patients met criteria for inclusion (8 SF, 2 VF). Median age was 45 years. About 90% were male, 60% were active intravenous drug abusers, and 100% had bacteremia (most commonly Enterococcus), with 50% of the patients having single-valve disease and 50% of the patients multivalvular disease. Total 90% had preserved cardiac function [ejection fraction (EF) > 40%]. All patients had splenic abscess diagnosed on HD 1, with 40% undergoing preoperative angioembolization. There was no difference in mortality between the groups (SF 25% vs VF 0%). There was no difference in the splenectomy portion of the operation, regardless of preoperative angioembolization. Conclusions: Representing the largest modern case series on the topic, a 25% overall 6-month mortality rate was observed; however, there was no difference in the order of operation noted in our population. Splenic abscess in conjunction with IE is a highly mortal combination; therefore, a large-scale multi-institutional approach should be utilized to delineate this population and address the order of operation as well as the role of splenic angioembolization in this subset of patients.