The fractionation efficiency of hollow fiber membranes (HFM) for milk protein fractionation was compared to ceramic tubular membranes (CTM) and spiral wound membranes (SWM). HFM combine the features of high membrane packing density of SWM and the more defined flow conditions and better control of membrane fouling in the open flow channel cross-sections of CTM. The aim was to comparatively analyze the effect of variations in local pressure and flow conditions while using single industrially sized standard modules with similar dimensions and module footprints (module diameter and length). The comparative assessment with varied transmembrane pressure was first applied for a constant feed volume flow rate of 20 m3 h−1 and, secondly, with the same axial pressure drop along the modules of 1.3 bar m−1, similar to commonly applied crossflow velocity and wall shear stress conditions at the industrial level. Flux, transmission factor of proteins (whey proteins and serum caseins), and specific protein mass flow per area membrane and per volume of module installed were determined as the evaluation criteria. The casein-to-whey protein ratios were calculated as a measure for protein fractionation effect. Results obtained show that HFM, which so far are under-represented as standard module types in industrial dairy applications, appear to be a competitive alternative to SWM and CTM for milk protein fractionation.