BACKGROUNDMembrane technology is an attractive alternative to conventional water/wastewater treatment technologies as it is sustainable and can be used as an independent process as well as being a part of integrated systems with other treatment technologies. Notwithstanding the abundant benefits that membrane‐based systems offer, their commercial application is overshadowed by the ubiquitous fouling. However, accurate prediction and identification of membrane fouling mechanisms can help to open new doors in recognition of appropriate arrangements for developing more effective membrane synthesis methods and fundamental strategies to achieve better performance, especially in large‐scale production.RESULTSIn this study, three fouling models, namely resistance‐in‐series (RIS), Hermia's and combined cake filtration–pore blockage models, were applied to precisely analyze fouling behavior in dead‐end microfiltration (MF) of collagen solution, as model foulant, using pure high‐density polyethylene and modified high‐density polyethylene membranes. The RIS model was shown to be not representative of the real fouling mechanism in MF membrane units. Similarly, none of the classical models were able to accurately predict fouling in the entire MF process. However, the combined cake–intermediate blockage model provided excellent fits for the membranes.CONCLUSIONSObtained results also demonstrated that physical cleaning was not enough for organic fouling elimination in MF processes. Finally, computational results were validated with experimental observations of collagen rejection and field emission scanning electron microscopy analyses as well. © 2020 Society of Chemical Industry