Microfiltration (MF) is increasingly used for the separation of casein micelles from serum or whey proteins (SP) in milk, using a 0.1–0.2 µm pore size membrane. One of the processing benefits of casein concentration by MF is that the co-product generated is considered as native or ideal whey. Ceramic graded permeability (GP) MF membranes ensuring long-term permeation flux and membrane selectivity have been successfully used for the separation of caseins from milk. Polymeric spiral wound (SW) MF membrane elements have also been reported to perform casein separation from milk but their performance has not yet been fully characterized. The objective of the present study was to compare the performance of 2 MF membranes configurations (SW vs GP) for the separation of casein from skim milk. The first membrane studied was a ceramic Membralox GP (model EP1940, Pall Corp.) with a 0.1-µm pore size and a surface area of 0.72 m² while the second was a polymeric polyvinylidene fluoride (PVDF) spiral-wound membrane (model V0.2–2B-3838, Synder filtration) with a 0.2 µm pore size and a surface area of 14.12 m² (2 elements). Both membranes were mounted on a Model 393 pilot-scale system (Tetra Pak, Champlin, MN). Experiments were performed at 50°C up to a concentration factor of 2×, 3×, and 4×. Permeation flux and changes in membrane resistance during MF were compared. Membrane selectivity (separation of caseins from whey proteins) was determined by chemical analysis (TN, NCN, NPN) and validated by SDS-PAGE electrophoresis. It was found that GP membrane had an average permeation flux 3 times higher than that of SW. The CN/TP ratio of the final retentates were similar for both membranes. The water flux of fouled membranes (before cleaning) was 40% and 60% of the initial water flux for SW and GP membrane respectively. Although casein separation could be achieved using the 2 membrane configurations (GP and SW), our observations suggest that the GP MF membrane offers better process control by maintaining a higher permeability and preventing severe membrane fouling upon casein separation from milk.