A modified Guggenheim quasichemical method (MGQ) has been applied to calculate enthalpies of mixing in mixtures based on chlorinated polymers such as poly(epichlorohydrin) (PECH) or poly(vinyl chloride) (PVC). The required parameters have been determined from experimental heats of mixing in mixtures of model compounds. Using the MGQ method, enthalpies of mixing of PECH/ester containing polymer mixture’s and PVC/polyoxide blends have been simulated. In PECH/ester containing polymer blends, the MGQ method gives an adequate picture of the evolution of the miscibility with the polyester CH2/CH2COO ratio. Similarly, in PVC/polyoxide blends, the variation of the heat of mixing along the polyoxide family seems to agree with the miscibility window of these blends. However, in PVC/poly(ethylene oxide) blends, the MGQ method was not able to predict accurately the experimentally observed dependence of the miscibility on the composition.