Cold flow, by definition is the migration of adhesive beyond the boundaries of the transdermal drug delivery system (TDDS). It can result in poor transdermal product performance on the skin, decrease in the drug flux across the skin and undesirable drug exposure. These problems usually show up on storage and can only be detected by stability studies. However, once a transdermal product is approved, a company typically does not test the stability of every production batch. Hence, the first aim of this study was to investigate the relationship between the cold flow degree and the physical-mechanical properties of the TDDSs. The second aim was to investigate the feasibility of near infrared spectroscopy (NIRS) to quantitatively predict cold flow. For this study, Durotak87-4098® was selected as a model pressure sensitive adhesive (PSA). Triacetin and triethyl citrate were used as plasticizers, respectively, mixing with Durotak87-4098® to formulate the prototype transdermal products. Thermally induced cold flow studies, static/dynamic shear adhesion tests and a pressure induced cold flow study were conducted to understand the relationship between the product shear adhesion and cold flow degree. A near infrared (NIR) model was developed; shear adhesion testing data and the amount of induced cold flow were used as the reference values to calibrate the model. This study shows that plasticizer content in a PSA can affect the product shear adhesion; the product shear adhesion is highly related to the cold flow degree. The NIR data was analyzed by using a series of chemometric methods like principal components analysis (PCA) and partial least square regression (PLS) showing that the NIR spectroscopy is able to quantitatively predict the shear adhesion of the transdermal product at the time of production.