BACKGROUND: Administration of oral nutritional supplements (ONS) inside hemodialysis (HD) units before sessions is an increasingly adopted option. Our aim was to assess the effects of predialytic ONS on nutritional status and quality of life (QOL) in HD patients. METHODS: One hundred HD patients were enrolled in this prospective, multicentric randomized clinical trial. Patients were assigned to receive ONS (25 gm protein powder) 1 h prior to the start of the HD session (predialytic) or maintained on their routine nutrition regimen for 3 months. RESULTS: At study end, supplemented patients showed a significant increase in serum albumin (p <
0.001), and a non-significant decrease in the median subjective global assessment (SGA) score. While in the control group, serum albumin remained stable, and the median SGA score increased significantly (p <
0.001). Body mass index and anthropometric measures did not differ between both groups. The supplemented patients showed significant improvement in three subscales of the Kidney Disease Quality of Life-36, without a significant change in QOL in control patients. Supplemented patients had significantly higher blood pressure (BP) (p = 0.037), lower urea reduction ratio (p = 0.020) and Kt/V (p = 0.021), higher serum calcium, lower total cholesterol and lower CRP (p = 0.047) levels compared to controls. There was no significant difference between groups regarding serum sodium, potassium, or phosphorus or adverse events. CONCLUSIONS: Predialytic ONS administration may contribute to improvements in serum albumin, and QOL. The effects on BP, CRP, and the reduction in dialysis adequacy, should be carefully considered while adopting such strategy. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT05952570. FIRST REGISTRATION DATE: 2/07/2023.