High performance, solution processable semiconductors are critical to the realization of low cost, large area electronics. We show that a signature molecular packing motif-side-chain interdigitation-correlates to high performance for a large and important class of organic semiconductors. The side chains of recently developed high performance copolymers of poly(alkylthiophenes) can and do interdigitate substantially, whereas they do not in the most common form of the extensively studied, lower performance poly(alkythiophenes). Side-chain interdigitation provides a mechanism for three-dimensional ordering; without it, poly(alkylthiophenes) are limited to small domains and poor performance. We propose the synthetic design rule that three-dimensional ordering is promoted by side-chain attachment densities sufficiently low to permit interdigitation.