Neutrophil percentage-to-albumin ratio (NPAR) has been proven to correlate with the poor prognosis of various diseases. This study aims at investigating the prognostic value of NPAR for septic cholangitis patients from Medical Information Mart Intensive Care IV database (MIMIC-IV).Overall, 329 adult septic cholangitis patients were retrospectively included, of whom 82 experienced deaths within 30 days. Cox regression, restricted cubic spline, as well as Kaplan-Meier curves were employed to evaluate the association between NPAR and 30-day mortality. Hazard ratio (HR) and 95% confidential interval (95% CI) were calculated. Receiver operating characteristic (ROC) curves and integrated discrimination improvement (IDI) analysis were utilized to assess the predictive efficacy of NPAR.NPAR was significantly associated with 30-day mortality in multivariable Cox analysis (HR = 1.52, 95%CI = 1.16-1.99, P = 0.003). Kaplan-Meier curves indicated NPAR in the second quartile (range from 2.55-2.93) demonstrated the lowest mortality (log-rank test: P < 0.001). RCS curves showed a U-shaped relationship between NPAR and 30-day mortality, and an inflection point of appropriately 2.73 was discovered. HRs and 95%CIs on the left and right sides of the inflection point, were 0.299 (0.114-0.781, P = 0.014) and 1.955 (1.362-2.807, P < 0.001), respectively. NPAR exhibited a moderate AUROC (0.668) for the prediction of 30-day mortality. Importantly, addition of the NPAR into illness score models can significantly improve the predictive ability.A U-shaped nonlinear association was observed between NPAR and 30-day all-cause mortality in septic cholangitis patients. NPAR emerged as a potential marker for the prognosis of critical cholangitis patients.Copyright © 2025 by the Shock Society.