Introduction Indoxyl sulfate (IS) and p cresyl sulfate (PCS) are protein bound toxins which accumulate with chronic kidney disease. Haemodiafiltration (HDF) increases middle molecule clearances and has been suggested to increase IS and PCS clearance. We therefore wished to establish whether higher convective clearances with HDF would reduce IS and PCS concentrations. Methods We measured total plasma IS and PCS in a cohort of 138 CKD5d patients treated by On-line HDF (Ol-HDF), by high pressure liquid chromatography. Findings Mean patient age was 64.66 16.5 years, 60.1% male, 57.3% diabetic, median dialysis vintage 25.9 months (12.4–62.0). The mean ICS concentration was 79.8656.4 umol/L and PCS 140.36101.8 umol/L. On multivariate analysis, IS was associated with serum albumin (b 4.31,P<0.001), and negatively with residual renal function (b-4.1,P50.02) and vegetarian diet(b-28.3, P50.048) and PCS negatively with log C reactive protein (b-75.8, P<0.001) and vegetarian diet (b-109, P50.001). Vegetarian patients had lower IS and PCS levels (median 41.5 (24.2–71.9) vs. 78.1 (49.5–107.5) and PCS (41.6 (14.2–178.3) vs. 127.3 (77.4–205.6) mmol/L, respectively, P<0.05. Vegetarian patients had lower preOl-HDF serum urea, and phosphate (13.8 63.8 vs. 18.465.2 mmol/L, and 1.3360.21 vs. 1.5860.45 mmol/L), and estimated urea nitrogen intake (1.2560.28 vs. 1.6260.5 g/kg/day), respectively, all P<0.05. Discussion Plasma IS and PCS concentrations were not lower with Ol-HDF compared to previous studies in haemodialysis patients. However those eating a vegetarian diet had reduced IS and PCS concentrations. Although this could be due to differences in dietary protein intake, a vegetarian diet may also potentially reduce IS and PCS production by the intestinal microbiome