Heavy haul railway operations permit the transport of huge volumes at lower cost than other modes of transport. The low cost can only be sustained if the maintenance costs associated with such railway operations are minimised. The maintenance costs are mainly driven by wheel and rail damage in the form of wear and rolling contact fatigue (RCF). Low wear rates in the wheel-rail interface have resulted in an increase in the prevalence of rail RCF, thereby increasing rail maintenance costs. The aim of this study is to develop an approach to reduce rail RCF on South Africa’s iron ore export line by managing the worn wheel shape. This approach is developed by evaluating wheel and rail profile shapes that contribute the most to RCF initiation, studying the influence of suspension stiffness and rail profile changes as well as a redesign of the wheel profile. The influence of wheel and rail profile shape features on the initiation of rolling contact fatigue (RCF) cracks was evaluated based on the results of multibody vehicle dynamics simulations. The damage index and surface fatigue index were used as two damage parameters to assess the influence of the different features. The damage parameters showed good agreement to one another and to in-field observations. The wheel and rail profile shape features showed a correlation to the predicted RCF damage. The RCF damage proved to be most sensitive to the position of hollow wear and thus bogie tracking. RCF initiation and crack growth can be reduced by eliminating unwanted shape features through maintenance and design and by improving bogie tracking. Two potential mitigation measures had been adapted from those published in literature to reduce RCF. The mitigation measures involved changes in suspension stiffness to spread wheel wear across the tread and the use of gauge corner relief rail profiles. These mitigation measures were evaluated by means of multibody dynamics and wear maintenance costs. These mitigation measures, however, did not prove to be successful in reducing RCF initiation while maintaining a low wheel wear rate. The current operating conditions on South Africa’s iron ore line, although still not optimal overall, were found to be better in terms of their wear and RCF performance than the two proposed RCF mitigation measures. Based on the finding of the study on two RCF mitigation measures it was recommended that a conformal wheel profile be developed to spread the wheel wear across the tread to reduce the occurrence and propagation of RCF cracks, while still maintaining low wheel wear rates. A comparative study of this new wheel profile design and the current wheel profile design was therefore performed using multibody dynamics simulation together with numerical wheel wear and RCF predictions. The advantages of the conformal wheel profile design were illustrated by evaluating the worn shape and resulting kinematic behaviour of the conformal design. The conformal design had a steadier equivalent conicity progression and a smaller conicity range compared with the current wheel profile design over the wheel’s wear life. The combination of a conformal wheel profile design with 2 mm hollow wear and inadequate adherence to grinding tolerances often result in two-point contact, thereby increasing the probability of RCF initiation. The conformal wheel profile design was shown to have many wear and RCF benefits compared with the current wheel profile design. However, implementation of such a conformal wheel profile must be accompanied by improved rail grinding practices to ensure rail profile compliance. Based on these findings an approach is proposed where the conformal wheel profile design together with improved compliance of the in-service rail profiles to the target rail profile are implemented. This has the potential to reduce RCF initiation on South Africa’s iron ore export line.