The fabrication and the optimization of photovoltaic solar cells based on poly(3,3-didodecylquaterthiophene) (12-PQT) blended with [6,6]-phenyl-C61 butyric acid methyl ester (PCBM) are reported. On the one hand, the effect of the blend composition shows the necessity to increase the amount of fullerene derivative compared to conventional poly(3-hexylthiophene)-based systems. On the second hand, thermal annealing of devices is optimized and discussed. Overall, in this work, the highest power conversion efficiencies are shown in the range of 0.3–0.4% which represents a lower value than that reported with poly(3-hexylthiophene). Results are discussed in terms of charge carrier mobility and phase segregation in this bicontinuous donor-acceptor network.