Recently, water-gated organic field-effect transistors (WGOFET) have been intensively studied for their application in the biological field. Surprisingly, a very limited number of conjugated polymers have been reported so far. Here, we systematically explore a series of polythiophene derivatives, presenting different alkyl side chains lengths and orientation, and characterized by various morphologies: comparative evaluation of their performances allows highlighting the critical role played by alkyl side chains, which significantly affects the polymer/water interface capacitance. Reported results provide useful guidelines towards further development of WGOFETs and represent a step forward in the understanding of the polymer/water interface phenomena.