In this work, the effect of crystallographic orientations and the strengthening due to grain/twin boundaries were investigated by uniaxial compression of single- and bi-crystal micropillars of pure zirconium (Zr) with ≥99.9% purity. Micropillars fabricated using focused ion beam (FIB) milling were compressed using a flat punch tip in a nanoindenter to obtain stress–strain curves for individual orientations of Zr. Only near-basal-oriented samples were deformed by multiple slip, while samples with other orientations were deformed by a single slip. Bi-crystal samples had significantly higher flow stress than single-crystal samples–the increment in flow stress arising from grain boundaries being higher than that arising from twin boundaries. Our analysis shows that while twin-boundary strengthening can be explained based on a size effect according to the Hall-Petch equation, the higher strengthening effect of grain boundaries appears to arise from a combination of a sample-size effect as well as dislocation accumulation at boundaries. © 2020 Informa UK Limited, trading as Taylor & Francis Group.