Background <p>Splenic infarction is a rare and often underrecognized condition with diverse etiologies and variable clinical presentations. While most cases are managed conservatively, identifying patients who may require surgical intervention remains a clinical challenge. This study aimed to evaluate the infarct-to-spleen volume ratio (ISR) as a radiologic predictor for splenectomy in patients with splenic infarction and to propose a risk stratification model incorporating ISR and fever.</p> Methods <p>In this retrospective, two-center cross-sectional study, 236 patients diagnosed with splenic infarction between January 2015 and January 2023 were included. Volumetric analysis was performed using contrast-enhanced CT to calculate ISR. Clinical, laboratory, and radiologic features were compared between surgical (<i>n</i> = 13) and non-surgical (<i>n</i> = 223) groups. ROC curve and logistic regression analyses were used to evaluate predictive parameters for splenectomy. A risk score based on ISR and fever status was developed to stratify patients into risk categories.</p> Results <p>The splenectomy rate was 5.6%. Patients who underwent splenectomy had significantly higher ISR (median 28.2 vs. 9.17, <i>p</i> = 0.02). ROC analysis identified ISR as a strong predictor for surgery (AUC = 0.69, 95% CI: 0.49–0.86), with a specificity of 77.9% and NPV of 97.2%. Multivariate logistic regression confirmed ISR (OR: 1.03, <i>p</i> = 0.002) and fever (OR: 2.69, <i>p</i> = 0.005) as independent predictors. A risk score (range 0–4) based on these variables stratified patients into low-, intermediate-, and high-risk groups with splenectomy rates of 1.5%, 6.3%, and 33.3%, respectively.</p> Conclusion <p>ISR is a novel, objective predictor of the need for splenectomy in patients with splenic infarction. Incorporating ISR and fever into a simple risk score may aid clinical decision-making and help identify candidates for early conservative management or outpatient follow-up.</p>