Using novel time-dependent ATR-FTIR technique and two-dimensional correlation analysis (2Dcos), the migration behavior of drugs with varying water solubilities was investigated with ethyl cellulose (EC) films prepared with different kinds of pore formers and/or plasticizers. Three major stages were determined for drug migration: (1) water migrated from the drug-saturated solution to the other side of the EC film, (2) upon saturation of the film, water migration ceased and enough pore former was dissolved, and (3) upon dissolution of enough pore former, channels were formed between both sides of the EC film causing drug migration to begin and water migration to return. Further investigations demonstrated a reduction or elimination in second stage with increasing water solubility of the pore former and/or decreasing water solubility of the drug. These results offer a mechanistic understanding of water and drug migration across EC films not previously studied and might provide an effective guide for the preparation of EC pharmaceutical coating with desired drug release behavior.