Poly(ethylene oxide) (PEO), a widely known flocculation agent used primarily as a fines retention aid in mechanical grade papers, has its efficiency enhanced by various compounds, known as cofactors. These cofactors form a complex with PEO, which acts as an efficient bridging agent for fines flocculation. The nature of the PEO/cofactor complex is mainly unknown, and it was originally believed that the association was driven by hydrogen bonding. Therefore it was decided to investigate the complex formation in more detail. As a model system we studied PEO and a model cofactor, corilagin, a precursor of tannic acid, a known cofactor for PEO. We performed both Semi-Empirical Molecular Orbital (PM3) gas phase calculations and Molecular Dynamics (MD) calculations in the presence of water. Both methods lead to the same surprising conclusion: no association between PEO and corilagin occurs at room temperature. The reason is that the gain of association enthalpy is not large enough to overcome the loss in entropy. No correlation was found between the association enthalpy and the number of hydrogen bonds between PEO and corilagin. The absence of PEO/corilagin complexation was confirmed by NMR, isothermal titration calorimetry and the inability of PEO/corilagin to flocculate MCC (microcrystalline cellulose). In the presence of low concentrations of salt, complexation and MCC flocculation was observed.