Abstract: A method of real-time markerless measurement and calibration of a patient positioning system includes computing a three dimensional point cloud representation of a patient by using a camera to obtain depth points of the patient, where the z-direction corresponds to a direction along the focal length of the camera, demanding a z-limit that corresponds to a lower (z-min) and an upper (z-max) specification, computing a point cloud covariance and a point cloud mean for an optimized principle components analysis to compute a torso topography of the patient, determining a center point of the point cloud as an anchor measurement region and using the camera to determine a distance to the patient to establish an angle between a patient torso and a vector that is perpendicular to the camera, averaging the depth measurements in reference regions and compensating for parallax error in real-time during a calibration measurement or radiotherapy treatment plan.