Distribution networks such as vasculature systems or urban transportation pathways are prevalent in our world. Understanding how different kinds of transport systems are organized to allow for efficient function in their environments and in the presence of constraints on material costs is currently an open area of investigation. In this study, we use methods from network science to compare and contrast the structure of two different classes of biological distribution networks: mycelial fungi and rodent brain vasculature. While each of these systems have been studied separately, less work has focused on understanding the diversity of their network organization. Here, we first examine several measures that characterize network connectivity on varying scales, finding that—although both systems have highly constrained network layouts—there are quantifiable differences in their architectures. Furthermore, using network analyses that specifically consider the embedding of these transport networks into real space, we observe that the two types of systems display distinct tradeoffs in network correlates of material cost, efficiency, and robustness. Together, our results provide evidence that while different distribution networks have general resemblances, they also exhibit variable design features that could reflect differences in their functions, environmental conditions, or development. Papadopoulos L, Blinder P, Ronellenfitsch H, Klimm F, Katifori E, Kleinfeld D, et al. (2018) Comparing two classes of biological distribution systems using network analysis. PLoS Comput Biol 14(9): e1006428. https://doi.org/10.1371/journal.pcbi.1006428 Source: journals.plos.org