Objectives:  End-stage renal disease (ESRD) patients starting renal replacement therapy are at risk of higher mortality than the general population, even in the first few months after the initiation of dialysis. Recently, several studies proposed that growth differentiation factor-15 (GDF-15) is a possible biomarker for the prognosis of patients on maintenance hemodialysis. Since GDF-15 levels were reported to have an inverse correlation with serum albumin, we investigated the predictive value of serum GDF-15/Albumin ratio on two-year mortality in ESRD patients initiating maintenance hemodialysis. Methods:  This was a single center retrospective study on ESRD patients who started maintenance hemodialysis at Chungnam National University Hospital between May 2014 and August 2019 with a follow-up of at least two years. All patients completed laboratory test and bioimpedance spectroscopy (BIS) prior to the initiation of the first dialysis. To compare the volume state between patients, the hydration state was normalized to overhydration/extracellular water (OH/ECW) and OH/ECW>15% was considered overhydrated. Kaplan-Meier analysis and Log-rank test were applied for survival analysis. Results:  The patients were stratified into quartiles according to the serum GDF-15/Albumin ratio. Among the 159 patients, the mean age was 61.78 ± 12.52 years and median survival was 20.03 ± 7.73 months. The highest GDF-15/Albumin quartile was significantly more associated with the increased risk of all-cause mortality than other quartiles (unadjusted hazard ratio (HR): 8.468, 95% confidence interval: 2.981–24.054, p<0.001). Older age and a higher overhydration state were associated with higher GDF-15/Albumin ratio. The ROC analysis confirmed that the ability of the GDF-15/Albumin ratio to predict mortality was superior to GDF-15 or albumin alone.  Conclusions:  In conclusion, the GDF-15/Albumin ratio measured at the initial maintenance hemodialysis is an independent prognostic marker of two-year mortality in ESRD patients.