In the first part of this paper, we present a model that explains and determines quantitatively the twists between nucleation islands in the case of a Volmer–Weber heteroepitaxial growth of tetrahedrally coordinated semiconductors along hexagonal orientations. These twists are caused by the network of the screw components of the 60° misfit dislocations. The orientations of the screw components are distributed randomly, and the maximum twist is obtained when all the screw components have the same orientation. The maximum twists are related to the density of misfit dislocations and, therefore, increase with the mismatch between the deposited materials and their substrate. In the second part of the paper, we study five systems having a large distribution of mismatches from 4% to 19%. For the four systems fulfilling the conditions necessary for the application of the model (plastic relaxation of grown islands), the measured maximum twists fit with the calculated values, thereby validating the model. The twists of nucleation islands are related to the mismatch and are, therefore, intrinsic to the material systems. The defects created at the coalescence of twisted islands determine the initial microstructure/defect distribution of the nucleation layer.