The relationship between co-nonsolvency of poly(N-isopropylaaylamide) (PNIPA) and the reentrant swelling transition of PNIPA gels in solvent mixtures was studied using a molecular thermodynamic framework based on the modified double lattice (MDL) theory of mixing and the Flory-Rehner (FR) chain model for elasticity. A secondary lattice concept of specific interactions was employed to correlate binary water/PNIPA solutions, and composition dependence of the energy parameter was adopted to describe the co-nonsolvency of the ternary solutions. The swelling equilibrium of crosslinked PNIPA gels was calculated using molecular interaction parameters obtained from lower critical solution temperature (LCST) transition behaviors of non-crosslinked PNIPA solutions. We applied the proposed method to PNIPA solutions containing methanol, acetone, dioxane (DO), tetrahydrofuran (THF), and poly(ethylene glycol) (PEG). Our results agreed with experimental reentrant and reentrant-convex type swelling data based on few adjustable parameters. In addition, the partitioning of solvent mixtures inside and outside the PNIPA gels as successfully predicted, which is significant for the application of hydrogels. The method presented here provides a theoretical basis for understanding the equilibrium behaviors of polymers and polymer gels in solvent mixtures. (C) 2013 Elsevier Ltd. All rights reserved.