In this work, the recently proposed Functional-Segment Activity Coefficient (F-SAC) model (Ind. Eng. Chem. Res., DOI: 10.1021/ie400170a) is extended for mixtures where hydrogen bonds (HB) can form. The F-SAC model is based on the concept of functional groups with the group interaction energies calculated according to the COSMO-RS theory. In the extension proposed here, hydrogen bonds are described by one additional energy parameter for each HB donor acceptor pair. The F-SAC parameters for substances not participating in hydrogen bonds were kept unchanged. Additional parameters were calibrated for 25 HB donor acceptor pairs by using infinite dilution activity coefficient (IDAC) data complemented by VU data for the ethanol/water system. For the considered IDAC data set, the F-SAC fit was superior to the predictions obtained with UNIFAC (Do). Finally, the predictive strength of the model was assessed using vapor liquid equilibrium as well as water/alkane mutual solubility data not considered in the model fitting process. Similar to the performance for nonassociating systems, good agreement with experimental data was possible for several systems over the entire composition range, as well as in the prediction of azeotropes.