We report a mechanism for controlling conductance in polymer nanostructures. Poly(3-dodecylthiophene-2,5-diyl) (PDDT) nanostructures were directly written between gold electrodes using thermal dip pen nanolithography and then characterized in UHV. We find that the conductivity of a PDDT nanostructure can be increased by more than five orders of magnitude (from <10−4 to 10 S cm−1) by exposure to energetic electrons, and then repeatedly returned to a semi-insulating state by subsequent exposure to hydrogen. Based on systematic measurements complemented by calculations of electronic structure and electron transport in PDDT, we conclude that the conductance modulation is caused by H desorption and reabsorption. The phenomenon has potential applications in hydrogen sensing and molecular electronics.