Membrane fouling is a major limitation in efficient operation of nanofiltration (NF) plants. Calcium sulfate is a major player in the most severe type of fouling – scaling - in sulfate removal systems for oil fields seawater injection operations and brackish water softener for industrial use by NF. Despite the vast number of studies that have been published on the scaling by calcium sulfate NF, have not yet been elucidated the mechanisms of formation and chemical inhibition of the phenomenon. The aim of this work was to study experimentally and conceptually the mechanisms involved in the generation and treatment by inhibition and chemical removal of fouling of calcium sulfate in NF membrane. Mathematical models of interpretation techniques and mechanisms of inhibition and characterization of deposits formed were used, trying to correlate them with performance indicators of process. The supersaturated solutions in a laboratory scale system confirmed the severity of fouling by calcium sulfate. The analysis of behavior showed a decrease of flow in alternating dominance between the mechanisms of pore blocking and cake formation. The study showed that inhibition of the mechanisms of action of the anti-fouling SHMP become more efficient than EDTA in maintaining performance in permeability and selectivity. The autopsy of the membrane with SEM / EDS and XRD revealed mostly gypsum crystals. The calculation methodology and integrated analysis of performance parameters proved to be an important tool to seek the most efficient and convenient measures to control and reduce fouling.