Scale formation of soluble salts is one of the major factors limiting the performance of reverse osmosis (RO) membranes for desalination. In this study, a dynamic model based on the crystallization theory was developed to analyze the effect of CaSO4 scale formation on RO desalination process. Taking into consideration two mechanisms in scale formation including surface and bulk crystallization, the performance of RO filtration was predicted as a function of crossflow velocity, transmembrane pressure, permeate recovery, and operation mode. The model results indicated that RO fouling due to surface crystallization is important in batch filtration whereas both Surface and bulk crystallization is important in crossflow filtration. This is because concentration polarization is directly related to Surface crystallization. RO fouling due to bulk crystallization appeared to increase with increasing crossflow velocity and permeate recovery. The effects of background organic matters and antiscalant oil scale formation were quantified using the model. The effect of operating parameters on RO fouling and concentration polarization was explored based on the model analysis.