BACKGROUND: Intensive hemodialysis (HD) may have significant benefits. the role of extended hemodiafiltration (HDF) has gained interest. The study was to evaluate the acute effects of extended HD and HDF on response and solute removal. STUDY DESIGN: Randomized crossover trial. PARTICIPANTS: Stable patients with end-stage renal disease undergoing conventional HD. INTERVENTION: 13 patients randomly completed a single 4-hour HD (HD4), 4-hour HDF (HDF4), 8-hour HD (HD8), and 8-hour HDF a 2-week interval between study sessions. Between study sessions, received routine conventional HD treatments. OUTCOMES: Acute hemodynamic and uremic toxin clearance. MEASUREMENTS: Blood pressure and heart rate, wave analysis, cardiac output, and microvascular density by sublingual capillaroscopy, as well as relative blood volume and thermal variables, measured. Clearance and removal of uremic toxins also were studied. treatments showed more stability of peripheral systolic blood pressure during HD4, -21.7+/-15.6mm Hg; during HDF4, -23.3+/-20.8mm Hg; during -6.7+/-15.2mm Hg [P=0.04 vs HD4; P=0.08 vs HDF4]; and during HDF8, - Hg [P=0.004 vs HD4; P=0.008 vs HDF4]). A similar observation was found peripheral diastolic and central blood pressures. Cardiac output stable in extended sessions (change during HD4, -1.4+/-1.5L/min; during -1.6+/-1.0L/min; during HD8, -0.4+/-0.9L/min [P=0.02 vs HDF4]; and -0.5+/-0.8L/min [P=0.06 vs HD4; P=0.03 vs HDF4), in line with the relative blood volume slope in long dialysis. No differences in density were found. Energy transfer rates were comparable (HD4, 13.3+/- HDF4, 16.2+/-5.6W; HD8, 14.2+/-6.0W; and HDF8, 14.5+/-4.3W). Small- phosphate removal were superior during long treatments. beta2- fibroblast growth factor 23 (FGF-23) reduction ratios were highest in LIMITATIONS: Small sample size, only acute effects were studied. Treatment time, and not modality, was the determinant for the response. HDF significantly improved removal of middle molecules, with results in extended HDF.