Three types of tail-to-tail (PDCBTTT), head-to-tail (PDCBTHT), and head-to-head (PDCBTHH) regioisomeric polythiophene copolymers were synthesized by modification of the substitution positions of their alkoxycarbonyl side-chains. Chain conformation, and optical, electrochemical, morphological, and charge-transport characteristics of the polymers were significantly influenced by their regiochemistry. PDCBTHH showed an amorphous morphology due to strong steric hindrance between its head-to-head alkoxycarbonyl side-chains, resulting in the poorest performance in organic solar cells and transistors among three types. PDCBTHT had a regiorandom structure with both head-to-tail and tail-to-head linkages in a polymer chain. As determined by field-effect mobility measurements, a highly regioregular and planar PDCBTTT exhibited the highest hole mobility (mu = 0.065 cm(2) V(-1)s(-1)), which was two orders of magnitude higher than that of the regiorandom PDCBTHT. The highest photovoltaic performance was also measured for PDCBTTT:a fullerene acceptor (PC71BM), by maintaining the packed structures of pristine PDCBTTT polymers in the blend with PC71BM. Altering the topology of alkoxycarbonyl side-chains of the copolymers resulted in significant differences in crystalline morphologies and electrical properties and thus should be carefully considered in the molecular design of organic semiconductors.