An accurate method of correcting spatial distortion in digital fluoroscopy images has been developed for generating fluoroscopy-based large field of view images for computer-aided radiation therapy simulation. This method is applicable to arbitrary gantry rotations and arbitrary shifts of the image intensifier relative to the central axis of the x-ray beam. It is therefore suitable for conventional radiation therapy simulation techniques that involve the arbitrary positioning of the image intensifier by the operator. Spatial distortion is modelled as two image intensifier orientation-dependent components, the first resulting from the projection of the x-ray image onto the curved surface of the image intensifier front end, and the second produced by the image intensifier electron optics, interactions with external magnetic fields and the video system. A geometrical model approximates the first component. The second component is modelled by a third-order polynomial transformation. A weighted mean approach is employed to achieve accurate distortion correction when the image intensifier is oriented differently from the calibration orientations. Mean and maximum residual errors (measured in the plane of the isocentre) of 0.4 mm and 1.0 mm respectively have been achieved with just 48 calibration orientations in four dimensions (gantry rotation and lateral, longitudinal and vertical shifts of the image intensifier).