Two regiochemically defined polythiophenes containing thiazolothiazole acceptor unit were synthesized by palladium(0)-catalyzed Stille coupling reaction. The thermal, electrochemical, optical, charge transport, and photovoltaic properties of these copolymers were examined. Compared to P1 with head-to-head coupling of two middle thiophenes, P2 with head-to-tail coupling of two middle thiophenes exhibits 40 nm red shift of absorption spectrum in film and 0.3 eV higher HOMO level. Both polymers exhibit field-effect hole mobility as high as 0.02 cm(2) V(-1) s(-1). Polymer solar cells (PSCs) were fabricated based on the blend of the polymers and methanofullerene[6,6]-phenyl C71-butyric acid methyl ester (PC(71)BM). The PSC based on P1:PC(71)BM (1:2, w/w) exhibits a power conversion efficiency of 2.7% under AM 1.5, 100 mW cm(-2), two times of that based on P2:PC(71)BM. The higher efficiency is attributed to lower HOMO (-5.6 eV) and smaller phase separation scale in P1:PC(71)BM blend. Tiny change in thiophene connection of P1 and P2 lead to great difference in HOMO, phase separation scale, and efficiency of their photovoltaic devices. (C) 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 49: 4875-4885, 2011