Two P3HT isomers with branched alkyl side chains, P3EBT and P3MPT, are synthesized. The HOMO energy levels of P3EBT and P3MPT are −5.35 and −5.24 eV, respectively, which are significantly lower than that of P3HT with a linear side chain. The absorption edges of the two P3HT isomer films, especially those of P3EBT, are blue-shifted in comparison with that of P3HT. A PSC based on P3EBT:IC60BA (2:1 w/w) shows a high open-circuit voltage of 0.98 V, which is the highest Voc reported so far for polythiophene-based PSCs. A PSC based on P3MPT:IC70BA (2:1 w/w) exhibits a power conversion efficiency of 3.62% with a Voc of 0.91 V. P3MPT is suitable for the application in tandem PSCs.