Shape memory alloy (SMA) actuators can be integrated with a pulley system to provide mechanical advantage and to reduce packaging space; however, there appears to be no formal investigation of the effect of a pulley system on SMA structural or functional fatigue. In this work, cyclic testing was conducted on nickel-titanium (NiTi) SMA actuators on a pulley system and a control experiment (without pulley). Both structural and functional fatigues were monitored until fracture, or a maximum of 1E5 cycles were achieved for each experimental condition. The Taguchi method and analysis of the variance (ANOVA) were used to optimise the SMA-pulley system configurations. In general, one-way ANOVA at the 95% confidence level showed no significant difference between the structural or functional fatigue of SMA-pulley actuators and SMA actuators without pulley. Within the sample of SMA-pulley actuators, the effect of activation duration had the greatest significance for both structural and functional fatigue, and the pulley configuration (angle of wrap and sheave diameter) had a greater statistical significance than load magnitude for functional fatigue. This work identified that structural and functional fatigue performance of SMA-pulley systems is optimised by maximising sheave diameter and using an intermediate wrap-angle, with minimal load and activation duration. However, these parameters may not be compatible with commercial imperatives. A test was completed for a commercially optimal SMA-pulley configuration. This novel observation will be applicable to many areas of SMA-pulley system applications development.