Highly plasticized poly(vinyl chloride) membranes (200 parts per hundred resin, phr) form the basis of ion-selective electrodes. The effects that five different plasticizers with different chemical structures, polarities and molecular weights M(w)BAR have on modified mechanical properties such as strength, secant stiffness, toughness and ductility were examined by puncture testing. As a function of membrane thickness, strength, toughness, and secant stiffness increase, while ductility remains constant. For maximal membrane strength and toughness, plasticizer M(w)BAR should be roughly 1000. The optimal ratio of experimental plasticization level (phr(exp) = 200) to the minimal level required for complete plasticization (phr(min)) was found to be approximately 2. A ’tube’-like model for plasticizer interaction with polymer chains is proposed to explain the vast differences in the mechanical properties of membranes.