Abstract This study investigates uniaxial compression behavior of focused ion beam (FIB) manufactured [1 1 1] nickel (Ni) small-scale pillars, ranging in diameter from approximately 25 μm to below 200 nm, in order to examine the effect of crystallographic orientation on the mechanical properties. This study is unique from other micro-pillar studies in that the [1 1 1] orientation has a considerably lower Schmid factor, and has multiple slip systems available. The [1 1 1] Ni pillars show a strong increase in yield stress and work hardening with decreasing diameter. The relationship between yield stress and diameter ( σ y ∝ d −0.69) matches well with previous small-scale pillar studies. Strain hardening, which has been inconsistently observed in other micro-pillar studies, is found to be a function of both diameter and orientation. Although the precise mechanism for hardening is unknown, transmission electron microscopy reveals dislocations throughout the pillar and into the base material suggesting that dislocation interactions and deformation below the pillar play a role in the observed strain hardening. Furthermore, a slight crystallographic rotation of the pillar is observed likely contributing to the observed mechanical properties. By exploring the role of crystallography on the plastic deformation behavior, this study provides additional insight into the nature of the size effect.