In vitro tests with saline or plasma replacing the blood are generally used in the development of membranes and membrane modules for hemodiafiltration (HDF) and for quality control purposes. Theoretical models predicting performance of a hemodiafilter based on module geometry, membrane properties and operating conditions are needed, but are not yet available, to distinguish to what extent membrane properties and module fluid dynamics both affect module clearance. In this paper, we report on the development of a simple predictive model for hemodiafiltration which still accounts for those phenomena that most profoundly affect performance of hemodiafilters, such as: the dependence of mass transport coefficients on the actual flow conditions; concentration polarization; the actual water filtration flux along the hemodiafilter length. The model was validated with respect to data in literature. Model predictions for low to high molecular weight solute clearance were within 10% of experimental data when saline replaces the blood and within 20% when plasma replaces the blood, at blood flow rates ranging from 100 to 500 ml/min and net overall filtration flow rates from 0 to 60 ml/min. Under all conditions, the model predicted clearances were in better agreement with experimental data than those predicted by other, non-predictive models for HDF.