Intradialytic hypotensive episodes are deleterious for hemodialysis (HD) patients. Acetate-free biofiltration with profiled potassium (AFBK) dialysate concentration may improve their cardiovascular stability. The aim of the present crossover study was to compare intradialytic hemodynamic tolerance and biological parameters between online hemodiafiltration (olHDF) and AFBK. Ten frail HD patients (8 males) with a mean age of 66.71- ± 12.31 years were studied for three months on olHDF and AFBK. There was a significant reduction of the hypotensive episodes during the AFBK period compared to the olHDF period. Mean intradialytic systolic and diastolic blood pressures were significantly higher during the AFBK period. There was a significant postdialytic increase in serum sodium concentration with the AFBK compared to olHDF. The dry weight and ultrafiltration indices were significantly higher, and the Kt/V was significantly lower during the AFBK period. Serum albumin concentration significantly increased during the AFBK period. AFBK leads to a significantly improved intradialytic tolerance in hemodynamically instable HD patients.