Background: Patients dialyzed with equal eKt/V may have huge variations in their urea concentrations. Methods: Urea generation rate, distribution volume and renal clearance were determined in 205 hemodialysis sessions of 33 patients with double pool urea kinetic modeling using dialyzer clearance from online monitoring. From these data, optimized prescriptions were computed. Results: In simulated dialysis sessions, the HEMO standard-dose equivalent clearance was not sufficient to keep time-averaged concentration (TAC) and average predialysis concentration (PAC) of urea below the defined upper limits (20 and 30 mmol/l), if normalized protein catabolic rate (nPCR) was greater than 1.3 g/kg/day. Protein catabolic rate was taken into account in the optimized prescription by cutting high urea concentrations. Conclusions: If patients having high urea concentrations with conventional clearance will benefit from higher dialysis dose - an unconfirmed hypothesis - this approach helps in identifying those who need more than three sessions per week.