Objective To investigate the association of serum fetuin-A (Fetuin-A) and serum calcification propensity (quantified by calciprotein particle semi-maturation time, T50) with incident cardiovascular disease (CVD) events and post-event mortality in maintenance hemodialysis (MHD) patients, and to clarify the predictive value of Fetuin-A and T50 at different stages of the CVD course.  Method A total of 513 MHD patients treated at Cangzhou Central Hospital from January 2020 to December 2024 were included and followed up from baseline measurement to December 31, 2024. Baseline serum Fetuin-A and T50 levels were measured. According to tertiles, Fetuin-A was categorized into low, intermediate, and high Fetuin-A groups, while T50 was categorized into short, intermediate, and long T50 groups. The endpoints were incident CVD events and all-cause mortality after CVD events. Baseline characteristics were compared using the Kruskal-Wallis H test or χ² test. Gray’s test and Fine-Gray competing risk regression were used to analyze the association of Fetuin-A and T50 with incident CVD events. Kaplan-Meier analysis, Log-rank test, and multivariate Cox proportional hazards regression were used to evaluate the association of Fetuin-A and T50 with mortality risk of post-CVD event.  Results The median follow-up duration was 30.0 months (P25-P75: 18.0-44.0 months). Based on Fetuin-A tertiles, significant differences among the 3 groups were observed in age (H=42.136, P＜0.001), dialysis vintage (H=22.584, P＜0.001), diabetic kidney disease (χ²=11.256, P=0.004), previous CVD history (χ²=10.674, P=0.005), dyslipidemia (χ²=6.124, P=0.047), serum calcium (H=9.210, P=0.010), erythropoiesis-stimulating agent dose (H=8.270, P=0.016), intravenous iron use (χ²=7.501, P=0.024), body mass index (H=18.907, P＜0.001), albumin (H=32.514, P＜0.001), and C-reactive protein (H=48.762, P＜0.001). Based on T50 tertiles, significant differences among the 3 groups were observed in age (H=8.149, P=0.017), previous CVD history (χ²=7.755, P=0.021), hypertension (χ²=6.873, P=0.032), serum calcium (H=8.846, P=0.012), serum phosphorus (H=20.436, P＜0.001), intact parathyroid hormone (H=6.648, P=0.036), erythropoiesis-stimulating agent dose (H=7.726, P=0.021), albumin (H=13.816, P=0.001), and C-reactive protein (H=32.887, P＜0.001). Gray’s test showed that the cumulative incidence of incident CVD events differed significantly among the 3 groups of Fetuin-A tertiles (χ²=24.613, P＜0.001) and increased with decreasing Fetuin-A levels; it also differed significantly among the 3 groups of T50 tertiles (χ²=8.743, P=0.013) and increased with shorter T50. Fine-Gray competing risk regression showed that compared with the high Fetuin-A group, the low and intermediate Fetuin-A groups had higher risks of incident CVD events (low Fetuin-A group: sdHR=1.650, 95% CI: 1.090～2.510, P=0.019; intermediate Fetuin-A group: sdHR=1.820, 95% CI: 1.230～2.690, P=0.003),  whereas with the long T50 group as the reference, the short and intermediate T50 groups were not significantly associated with incident CVD events after adjustment for confounders and Fetuin-A (short T50 group: sdHR=1.210, 95% CI: 0.770～1.890, P=0.405; intermediate T50 group: sdHR=1.290, 95% CI: 0.880～1.890, P=0.192). Log-rank test showed no significant difference in cumulative mortality of post-CVD event between the combined low/intermediate Fetuin-A group and the high Fetuin-A group (χ²=1.892, P=0.169), whereas the combined short/intermediate T50 group had a higher cumulative mortality than the long T50 group (χ²=7.862, P=0.005). Multivariate Cox proportional hazards regression showed that the combined short/intermediate T50 group had a higher mortality risk of post-CVD event than the long T50 group (HR=3.240, 95% CI: 1.370～7.650, P=0.009), while no significant difference was observed between the combined low/intermediate Fetuin-A group and the high Fetuin-A group (HR=0.900, 95% CI: 0.380～2.160, P=0.810).  Conclusion Low Fetuin-A was mainly associated with an increased risk of incident CVD events during follow-up, whereas short T50 was mainly associated with an increased mortality risk of post-CVD event. Combined assessment of these two biomarkers may facilitate stage-specific stratification of CVD risk in MHD patients.