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Introduction/Objective. Most patients with end-stage renal disease (ESRD) have hypertension. However, dialysis-related strategies to optimize blood pressure in these patients remain controversial. The current study aims to investigate the influence of dialysate sodium profiling on ambulatory blood pressure (ABP) in patients on maintenance hemodialysis, when there are no adequate dialytic and economic resources or high patient compliance. Methods. This prospective, single-center study enrolled 60 hypertensive ESRD patients. Subjects received maintenance dialysis with regular dialysate sodium concentration (140 mmol/L) during the initial three months after the enrollment, and were randomly assigned to continue regular sodium dialysate (group A) or switch to sodium profiling (group B) for duration of three months. ABP, heart rate (HR), pre-/postdialysis serum sodium levels, antihypertensive treatment dosages, and interdialytic weight gain (IDWG) etc. were recorded after treatment assignment. Results. Thirty patients each were enrolled in groups A and B. The characteristics at baseline were not significantly different between the two groups. Compared to patients in group A three months later, patients in group B had lower systolic ABP (p = 0.00), HR (p = 0.04), IDWG (p = 0.04), and antihypertensive medication dosages (p = 0.04). Throughout the treatment duration, no significant inter-group differences were observed for pre-/post-dialysis serum sodium and intradialytic complications. Additionally, no significant correlations were found between systolic or diastolic ABP and other variables studied in this study. Conclusion. In this study, we found that dialysate sodium profiling successfully ameliorated hypertension and reduced BP medications without altering natremic levels or increasing complications among patients on maintenance hemodialysis during the three months. Dialysate sodium profiling was relatively safe in this duration.