This study investigated the performance of direct hollow fiber nanofiltration (dNF40) membranes from NX Filtration BV on a pilot scale for the treatment of pre-treated IJsselmeer water from Waterwinstation Prinses Juliana (WPJ) in Andijk, as well as the direct treatment of raw IJsselmeer water. The objective was to evaluate the long-term fouling potential and the retention of ions and natural organic matter (NOM) using both WPJ pre-treated IJsselmeer water and raw IJsselmeer water. Additionally, the rejection of organic micropollutants (OMPs) under artificially elevated conditions, referred to as ‘spiked solution’, using WPJ pre-treated IJsselmeer water was investigated. Limited to no fouling was observed on the dNF40 membrane during stable operation when treating both WPJ pre-treated IJsselmeer water and raw IJsselmeer water, even under changing process conditions. NOM removal consistently exceeded 90% regardless of process conditions or water type. The retention of per- and polyfluoroalkyl substances (PFAS) was above 80%, with even higher retention observed for higher molecular weight values. Low molecular weight pharmaceuticals, all below the molecular weight cut-off (MWCO) of the dNF40 membrane (400 Da), exhibited approximately 30% retention. The dNF40 membrane showed better retention of negatively charged pharmaceuticals in the spiked solution compared to positively charged and neutral pharmaceuticals. A total cost of ownership (TCO) analysis unveiled that operational expenditures (OPEX) were three times higher than capital expenditures (CAPEX) for a 5-stage full-scale dNF40 system. Among the components, membrane replacement costs constituted the majority of OPEX (68%), followed by energy costs (31%) and chemical costs (<1%). Overall, the study showcased the suitability of the dNF40 membranes for treating IJsselmeer water, achieving effective removal of NOM and PFAS.