BACKGROUND: Although low high-density lipoprotein cholesterol (HDL-C) is associated with poor outcomes in heart failure, its specific prognostic role in non-ischemic dilated cardiomyopathy (DCM) remains undefined. This study aimed to investigate the association between HDL-C levels and long-term clinical outcomes in patients with DCM. METHODS: We retrospectively enrolled 297 patients with DCM who underwent cardiac magnetic resonance between January 2017 and October 2024. The primary endpoint was a composite of all-cause mortality and heart transplantation; the secondary endpoint additionally included heart failure readmission. The associations between HDL-C and clinical outcomes were assessed using Kaplan-Meier analysis, Cox regression, restricted cubic spline (RCS), and sensitivity analyses. RESULTS: During a median follow-up of 35 months, 41 (13.8%) and 97 (32.7%) patients experienced the primary and secondary endpoints, respectively. Kaplan-Meier analysis demonstrated that patients with higher HDL-C had significantly better event-free survival for both the primary and secondary endpoints (log-rank P < 0.001 for both). In multivariable Cox regression models, lower HDL-C was consistently and independently associated with an increased risk of the primary (hazard ratio [HR] 0.19, 95% confidence interval [CI]: 0.05-0.68, P = 0.011) and secondary (HR 0.15, 95% CI: 0.07-0.34, P < 0.001) endpoints. After further adjustment for echocardiographically estimated pulmonary artery systolic pressure, the effect estimate for the association between HDL-C and clinical outcomes was attenuated (primary endpoint: HR 0.31, 95% CI: 0.08-1.11, P = 0.072; secondary endpoint: HR 0.19, 95% CI: 0.08-0.44, P < 0.001). RCS curves showed a linear relationship between HDL-C and both endpoints (P for nonlinearity > 0.05 for both). Sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: Lower HDL-C levels were independently associated with adverse outcomes in patients with non-ischemic DCM, an association partly attenuated by adjusting for pulmonary hypertension markers. As a readily available prognostic biomarker, HDL-C may inform risk stratification in this population.