Background: The FX class of haemodialysers features a new class of high-flux polysulfone membrane which has been suggested to induce less inflammation. Methods: This was a randomized, cross-over study performed on 33 haemodialysis patients. Patients were randomized to FX60 or HF80 dialysers for 3 months and then changed to the other dialyser. Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured at baseline, and every 3 months. The Kidney Disease Quality of Life Short Form was also administered. Results: The mean of the difference in the IL-6 level between dialysers was 1.4 ± 8.0 pg/ml (95% CI –1.8, 4.5 pg/ml). There was no significant difference in TNF-α (95% CI –0.35, 0.18 pg/ml) or CRP levels (95% CI –2.67, 6.20 mg/l). The quality of social interaction and role limitations caused by physical health problems were significantly higher with the FX60, p = 0.04 and 0.047, respectively. Conclusions: The FX dialysers do not result in a significant difference in the level of systemic inflammation compared to the HF80.