Background: Among the different endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic CRSwNP (ECRSwNP) exhibits more severe symptoms and a higher rate of recurrence compared with noneosinophilic CRSwNP (non-ECRSwNP), as well as distinct metabolic alterations. Hence, early identification of metabolic alterations in polyps is crucial for the prediction and selection of personalized treatment for patients with CRSwNP, especially ECRSwNP. However, clinical practice faces a deficiency in readily accessible and expedited predictive diagnostics of metabolic changes. Objective: This study aimed to assess the capacity of 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) concentrations in nasal secretions to classify endotypes and predict the recurrence of CRSwNP. Methods: Levels of 15(S)-HETE in nasal secretions were measured via enzyme-linked immunosorbent assay (ELISA) in 57 patients with ECRSwNP and 49 patients with non-ECRSwNP. The expression and distribution of ALOX15 were assessed by immunohistochemical staining. In addition, multivariate logistic regression analysis was conducted to identify predictive factors for polyp recurrence. The optimal cutoff value was determined as the point on the receiver operating characteristic (ROC) curve with the maximum Youden Index. Results: The concentration of 15(S)-HETE in nasal secretions was significantly higher in the ECRSwNP group (median [interquartile range (IQR)]: 294.34 ng/mL [83.23-701.34 ng/mL]) than in the non-ECRSwNP group (median [IQR]: 100.19 ng/mL [25.53-207.25 ng/mL]) (P < 0.0001). Furthermore, it was positively correlated with the eosinophil counts and percentage in nasal polyp tissue (r = 0.620, P < 0.001 and r = 0.487, P < 0.001, respectively). Multivariate logistic regression analysis showed that 15(S)-HETE in nasal secretions was a risk factor for the recurrence of CRSwNP (odds ratio = 1.004, 95% confidence interval = 1.001-1.008, P = 0.022), and the ROC curve showed a predictive value for recurrence of CRSwNP (area under the curve = 0.890, P < 0.001). Conclusion: 15(S)-HETE in nasal secretions, as measured by ELISA, can serve as a reliable and alternative indicator for identifying ECRSwNP and predicting CRSwNP recurrence.