Fluid dynamics and heat transfer of flow through periodic open-cellular microlattice structures are characterized for varying superficial flow orientations and flow rates to investigate heat transfer and pressure loss anisotropy. For given Reynolds number, friction factor is lowest when flow is aligned with the largest straight-through passages in the microlattice. A maximum friction factor, over twice the optimally aligned friction factor, exists for flow orientations between pi/8 and pi/4 rad off the optimal alignment, with little variation in friction factor for pi/8 and pi/4 rad. Heat transfer is maximized at pi/4 rad off axis from the largest straight-through passages; however, less angular variation occurs in Nusselt number than in friction factor. Empirical correlations involving superellipses yield analytical equations describing Nusselt number dependence on flow angle and Reynolds number. This work enables selection of optimal flow orientations and optimal cellular architecture in convective heat transfer implementations of microlattice materials for lightweight and multifunctional applications. (C) 2012 American Institute of Chemical Engineers AIChE J, 59: 622-629, 2013