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Dialysis adequacy is a known risk factor for mortality in maintenance hemodialysis (MHD) patients. However, the optimal dialysis dose remains controversial. Therefore, we aimed to explore the relationship between dialysis dose and all-cause and cardiovascular disease (CVD) mortality among MHD. We examined the associations of dialysis dose with mortality in a cohort (n = 558) of MHD patients from 31 December 2015 to 31 December 2020. Dialysis adequacy was assessed using baseline Single-pool Kt/Vurea (spKt/V), which was categorized into three groups, and the lowest dose group was used as the reference category. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. A total of 214 patients died (64.5% for CVD). Compared with the low-dose group, high-dose group could reduce the risk of all-cause mortality by 33% (HR = 0.67, 95% CI: 0.47–0.98). Of note, when stratification by age, high-dose group was associated with both lower all-cause (HR = 0.46, 95% CI: 0.26–0.81) and CVD mortality (HR = 0.42, 95% CI: 0.20–0.88) among patients with age below 65 years. When stratification by dialysis age, high-dose group was associated with decreased risk of CVD mortality (HR = 0.43, 95% CI: 0.20–0.91) among patients with dialysis age over 60 months. spKt/V is a simple index of hemodialysis dose used in clinical practice and a useful modifiable factor in predicting the risk of death, especially in MHD patients under 65 years old or dialysis age more than 60 months. [ABSTRACT FROM AUTHOR]