Aero-engine spline couplings are widely used in the aero-industry to transfer torque and power. They are often subjected to fretting wear damage which results in reduced equipment life and early replacement. This work focuses on experimental investigation to be used as a basis for predicting fretting wear in spline couplings working in a misaligned condition. For this purpose tests have been performed on spline couplings under varying conditions of torque and misalignment angles. The experimental data has been used to develop empirical relations and neural-network-based approximations for the prediction of fretting wear. Though the tests have been performed specifically on spline couplings of nitrogen-hardened 42CrMo4, the findings of this work are fairly general and may be used as a quick and early design tool for spline couplings of any material owing to their straightforward and simple application.