Purpose: Splenic abscess formation is a serious complication in the setting of active endocarditis, and splenectomy is recommended. However, the optimal timing for splenectomy is yet undetermined. The purpose of this study was to evaluate the role of a one-stage splenectomy and valve surgery for active endocarditis. Methods: Among 202 consecutive endocarditis patients, 18 had splenic lesions on preoperative abdominal screening, who underwent cardiac surgery and splenectomy as a one-stage procedure (group A) and were compared to patients with unremarkable abdominal screening (group B, n = 184) undergoing sole cardiac surgery. Results: No difference was observed regarding preoperative characteristics (age, gender, New York Heart Association [NYHA] grade, diabetes, coronary artery disease, redo surgery, adiposity, smoking), intubation time, and prolonged ventilation. There were 23 early postoperative deaths in group B (12.5%) vs. none in group A. At 180 days, survival was significantly higher for patients in group A (94.4%) vs. group B (67.9%, p = 0.016), although this difference did not reach statistical significance (log-rank test, p = 0.073). Multivariate Cox proportional hazards regression revealed age above 50 years (hazard ratio [HR] 3.327, 95% confidence interval [CI] 1.279-8.650) and NYHA class above III (NYHA III or IV: HR 3.117, 95% CI 1.119-8.683, p = 0.030; NYHA IV: HR 3.678, 95% CI 1.984-6.817, p < 0.001) as independent risk factors for mortality at 180 days. A trend towards a protective factor was observed for simultaneous splenectomy (HR = 0.171, 95% CI 0.023-1.255). Conclusion: Simultaneous valve surgery and splenectomy is an approach for active endocarditis complicated by splenic lesions with a low 180-day mortality. Despite the expected risk elevation by septic lesions and the additive trauma of a laparotomy, patients with simultaneous splenectomy had a favourable outcome regarding early mortality and mortality at 6 months.