The configuration of landmarks is an important issue in minimizing the target registration error (TRE). In this paper the effect of different landmark configurations on the accuracy of pedicle screw placement during image guided spine surgery (IGSS) is investigated. Since the spine is deformed in intra-operative conditions compared to the preoperative situation, an accurate alignment of each vertebra is crucial to compensate for the deformation. CT compatible markers are placed over anatomical landmarks which are feasible and routinely used in surgical procedures. The TRE is obtained directly for the markers which are placed on the right and left pedicle of the vertebra. The estimated TRE values are also calculated using Fitzpatrick’s TRE estimation formula. Optimum selections of landmarks are proposed for different number of landmarks, according to the minimum TRE values in different configurations. The approach uses feasible anatomical landmarks, is able to become adaptive to constraints that may be imposed by surgeons during surgical procedure and it is reasonably robust to outliers. The proposed configurations are then used as initial conditions for surface registration. After removing the markers, the corresponding points in CT images and physical space are aligned using singular value decomposition. Then, ICP algorithm is applied to perform surface registration of the vertebra. The results indicate that registration accuracy is highly affected by the number of landmarks used in the initial point based registration as well as their arrangement. According to the results an improvement of 40% in the TRE for the best possible configuration of landmark is obtained.