In this study, low-cycle fatigue (LCF) tests at 500 °C in the <001>, <011> and <111> directions have been performed for the Ni-based single-crystal superalloy MD2. All tests were carried out in strain control with R_ε=-1. The <001> direction has the lowest stiffness of the three directions and also shows the best fatigue properties in this study followed by the <011> and <111> directions, respectively. It is well recognised that Ni-based single-crystal superalloys show a tension/compression asymmetry in yield strength and this study shows that a tension/compression asymmetry also is prevalent during LCF conditions. At mid-life, the <001> direction generally has a higher stress in tension than in compression, while the opposite is true for the <011> direction. For the <111> direction the asymmetry is found to be strain range dependent. The <011> and <111> directions show a cyclic hardening behaviour when comparing cyclic stress-strain curves with monotonic stress-strain curves. In addition, the <011> and <111> directions show a serrated yielding behaviour for a number of cycles while the yielding of the <001> direction is more stable.