Background: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have antithrombotic, lipid-lowering and antiinflammatory properties. The aim of this study was to verify if dietary supplementation with omega-3 PUFAs is able to induce changes of blood pressure, nutritional and coagulative profile, inflammation and blood cell counts in patients on hemodialysis (HD). Methods: We designed a 12-month, prospective, single-blind, sequential intervention, cohort study. All of the HD patients undergoing HD in our unit were eligible for the study. Patients on HD for at least 6 months with an autologous vascular access were enrolled. No thresholds for blood pressure or lab parameters were considered. Patients taking nonsteroidal antiinflammatory drugs, steroids or statins or those with catheters, grafts, liver diseases, malignancies, malnutrition or sepsis were excluded. After the baseline evaluations the patients underwent 3 consecutive 4-month study periods taking the following supplements: A (olive oil: 2 g/day), B (omega-3 PUFA: 2 g/day), C (olive oil: 2 g/day). Results: Twenty-four patients met the inclusion criteria. All patients completed the follow-up. Fibrinogen, hemoglobin, platelet, red and white blood cell counts, parathormone (PTH), partial thromboplastin time (PTT), serum total cholesterol, triglycerides, apolipoprotein A and B, C-reactive protein (CRP) and albumin levels did not change significantly during the study. On the contrary, systolic (mean +/- SD) (A: 131 +/- 17.8 mm Hg; B: 122 +/- 12.8 mm Hg; C: 129 +/- 13.2 mm Hg), diastolic (A: 83 +/- 16.3 mm Hg; B: 72 +/- 14.8 mm Hg; C: 79 +/- 6.5 mm Hg) and mean blood pressure (A: 99 +/- 16.8 mm Hg; B: 88 +/- 14.1 mm Hg; C: 96 +/- 8.7 mm Hg) were significantly lower at the end of study period B (repeated measures ANOVA and Tukey's post hoc test: p<0.05). Conclusions: In our experience, blood pressure was the only parameter influenced by omega-3 PUFA supplementation in patients on long-term HD.