All 2D/3D anatomy based rigid registration algorithms are iterative, requiring an initial estimate of the 3D data pose. Current initialization methods have limited applicability in the operating room setting, due to the constraints imposed by this environment or due to insufficient accuracy. In this work we use the Microsoft Kinect device to allow the surgeon to interactively initialize the registration process. A Kinect sensor is used to simulate the mouse-based operations in a conventional manual initialization approach, obviating the need for physical contact with an input device. Different gestures from both arms are detected from the sensor in order to set or switch the required working contexts. 3D hand motion provides the six degree-of-freedom controls for manipulating the pre-operative data in the 3D space. We evaluated our method for both X-ray/CT and X-ray/MR initialization using three publicly available reference data sets. Results show that, with initial target registration errors of 117:7 ± 28:9 mm a user is able to achieve final errors of 5:9 ± 2:6 mm within 158 ± 65 sec using the Kinect-based approach, compared to 4:8±2:0 mm and 88±60 sec when using the mouse for interaction. Based on these results we conclude that this method is sufficiently accurate for initialization of X-ray/CT and X-ray/MR registration in the OR.