〔Abstract〕 To systematically evaluate the association between serum indirect bilirubin（IBIL）levels and the risk of stroke incidence in patients with cardiovascular-kidney-metabolic（CKM ）syndrome stages 0-3. Methods A total of 48，301 participants with CKM syndrome stages 0-3 were included，during which 2，904 stroke events were recorded. A prospective cohort study design was employed. Cox proportional hazards regression models were used to analyze the relationship between IBIL and stroke risk，and restricted cubic spline（RCS）re- gression was applied to examine the dose-response relationship. Threshold effect analysis was conducted to identify potential inflection points in nonlinear relationships. Results Multivariable Cox regression analysis showed that in the overall population，each 1 μmol/L increase in IBIL level was associated with approximately a 1. 2% reduction in stroke risk（HR = 0. 988，95% CI：0. 979–0. 996，P < 0. 05）. A significant interaction was observed between IBIL and CKM stages in relation to stroke risk（Pinteraction < 0. 05）. In individuals with stages 0–2 of CKM syndrome， higher IBIL levels showed a significant inverse association with stroke risk（Ptrend < 0. 05）；however，no such asso- ciation was observed in stage 3 patients. RCS regression and threshold effect analysis further revealed a nonlinear relationship between IBIL levels and stroke risk in stage 3 CKM patients（Plog-likelihood ratio < 0. 05）. When serum IBIL exceeded 10. 980 μmol/L，each 1 μmol/L increase was associated with approximately 5. 7% increase in stroke risk （HR = 1. 057，95% CI：1. 009–1. 107，P < 0. 05）. Conclusion The correlation between serum IBIL and stroke varies across different stages of CKM syndrome，showing a significant negative association in individuals at stages \ 0–2，while in stage 3 patients，it exhibits a threshold effect with an inflection point at 10. 980 μmol/L.