Background: Correction of metabolic acidosis in dialysis patients should be considered of paramount importance. However, consuming sodium bicarbonate tablets during the interdialytic interval to reach predialysis bicarbonate levels of 23–24 mmol/l is not widespread due to the fear of greater interdialytic weight gain and fluid overload. For this reason we investigated in a cross-sectional and in an interventional study the effect of oral sodium bicarbonate supplementation on body weight gain, plasma sodium concentrations and predialysis blood pressure in a group of stable uremic patients on regular hemodialysis (HD) treatment. Study Design: 110 patients (67 men, 43 women), mean age 67 ± 15 (range 22–89) years, on regular chronic HD treatment for 6–372 (median 48) months were studied. 70 patients were on regular oral bicarbonate supplementation for at least 4 weeks (group A), 40 patients were not on oral bicarbonate supplementation (group B). The following parameters were recorded: dry body weight (DBW), interdialytic weight gain (IWG), body mass index (BMI), plasma sodium (Na), serum pH, serum bicarbonate (sBic), K<sub>t</sub>/V, normalized protein catabolic rate (PCRn), predialysis systolic (SBP) and diastolic (DBP) blood pressure, and bicarbonate therapy (g/day). 18 patients not on oral bicarbonate supplementation with sBic levels ≤20 mmol/l were started on oral bicarbonate therapy and were prospectively followed in the context of an interventional study of correction of chronic metabolic acidosis. The same parameters were recorded before (pre) and after (post) 4 months of oral bicarbonate supplementation. Results:Serum pH and sBic concentrations were significantly higher in patients in group A compared to patients in group B (pH 7.37 ± 0.02 group A vs. 7.33 ± 0.02 group B: p <0.001: sBic 23.8 ± 1.4 group A vs. 20.9 ± 1.4 group B: p < 0.0001). Age, DBW, BMI, IWG, SBP, DBP, Na, K<sub>t</sub>/V and PCRn did not differ between groups. The mean daily dose of oral sodium bicarbonate administered to patients in group A was 1.9 ± 0.9 (range 1–5, median 2) g/day. Also in the 18 patients who started bicarbonate treatment, a significant increase in serum pH and sBic concentrations and a significant reduction in PCRn were observed. No significant change in DBW, IWG, SBP, DBP and Na concentrations after 4 months of treatment was found. Conclusions: Our data show that in stable uremic patients on regular HD treatment, oral daily administration of sodium bicarbonate is effective in correcting mild-moderate chronic metabolic acidosis, and does not cause increased interdialytic body weight gain, different plasma sodium concentrations and different systolic-diastolic blood pressure levels compared to patients not on oral sodium bicarbonate supplementation.