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Background. Longer and more frequent dialysis sessions have demonstrated excellent survival and clinical advantages, while online haemodiafiltration (OL-HDF) provides the most efficient form of dialysis treatment. The aim of this study was to evaluate the beneficial effects of a longer (nocturnal) and more frequent (every-other-day) dialysis schedule with OL-HDF at the same or the highest convective volume. Methods. This prospective, in-centre crossover study was carried out in 26 patients, 18 males and 8 females, 49.2 6 14 years old, on 4-5 h thrice-weekly post-dilution OL-HDF, switched to nocturnal every-other-day OL-HDF. Patient inclusion criteria consisted of stable patients with good vascular access and with good prospects for improved occupational, psychological and social rehabilitation. Patients were randomly assigned into two groups: Group A received the same convective volume as previously for 6 months followed by a higher convective volume for a further 6 months, while Group B received the same schedule in reverse order. Results. Nocturnal every-other-day OL-HDF was well tolerated and 56% of patients who were working during the baseline period continued to work throughout the study with practically no absenteeism. The convective volume was 26.7 6 2 L at baseline, 27.5 6 2 with the unchanged volume and 42.9 6 4 L with the higher volume. eKt/V increased from 1.75 6 0.4 to 3.37 6 0.9. Bicarbonate, blood urea nitrogen (BUN) and creatinine values decreased, while phosphate levels fell markedly with a 90% reduction in phosphate binders. Blood pressure and left ventricular hypertrophy (LVH) improved and the use of anti-hypertensive drugs decreased. In both groups, BUN, creatinine and b2-microglobulin reduction ratios improved. Different removal patterns were observed for myoglobin, prolactin and a1-acid glycoprotein. Conclusions. Nocturnal every-other-day OL-HDF could be an excellent therapeutic alternative since good tolerance and occupational rehabilitation, marked improvement in dialysis dose, nutritional status, LVH, phosphate and hy hypertension control and a substantial reduction in drug requirements were observed. In this crossover study, different removal patterns of large solutes were identified.