Background <p>The mortality following cardiac surgery remains high. The neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) is a marker that reflects both inflammation and metabolic status, and it has shown promise in predicting outcomes across various diseases. However, the association of NHR with the outcomes in cardiac sur gery patients has not been fully validated.</p> Methods <p>This retrospective cohort study analyzed data from the MIMIC-Ⅳ database, including 2784 patients who underwent cardiac surgery. Patients were categorized into three groups (Q1, Q2, Q3) based on the NHR value. The primary outcome was 90-day all-cause mortality. The secondary outcomes included 180-day and 360-day all-cause mortality. Kaplan-Meier survival analysis, Cox proportional hazards regression, and restricted cubic spline (RCS) analysis were employed to assess the relationship between NHR and all-cause mortality.</p> Results <p>A total of 2784 patients (73.10% male) were enrolled. Higher NHR index levels were associated with an increased risk of 90-day,180-day, and 360-day all-cause mortality as shown by Kaplan–Meier curves. Cox proportional hazards analysis showed that the elevated NHR index was significantly related to all-cause death. Additionally, restricted cubic spline (RCS) analysis confirmed a linear positive relationship between NHR and all-cause mortality.</p> Conclusion <p>NHR is significantly associated with all-cause mortality in patients undergoing cardiac surgery. As a simple and cost-effective measure, NHR can support clinicians in the early identification of high-risk patients and guide personalized postoperative management strategies. To confirm its clinical utility and improve postoperative risk assessment and patient care, further large-scale, multicenter retrospective cohort studies are needed.</p>