We have investigated the initial nucleation process of polythiophene derivatives by molecular dynamics simulations to elucidate the role of flexible side chains in the crystallization process. We considered poly(3-hexylthiophene) (P3HT), poly(3,3‴-dihexylquarterthiophene) (PQT6), poly(3-dodecylthiophene) (P3DDT), and poly(3,3‴-didodecylquaterthiophene) (PQT12), in which the lengths and densities of the alkyl side chains are different. In the case of the short side-chain molecules (P3HT and PQT6), the initial nucleation process is based on the following steps. At the beginning, the thiophene rings align and ordering of the main chains commences shortly afterward. Ordering of the flexible side chains is induced after formation of a stacked structure of rigid main chains. In the case of a long and dense side-chain molecule (P3DDT), the initial nucleation process shows different features. The ordering process of the thiophene rings or main chains becomes very slow, while that of side chains becomes fast. In addition, the local order of the main chains becomes lower than those of P3HT and PQT6. These simulation results reveal that long and dense side chains suppress the nucleation process, whereas long but low-density side chains lead to formation of stacked nuclei in a different manner from those observed for short side-chain molecules.