This paper presents a new algorithm for frame registration. Our algorithm requires only that the frame be comprised of straight rods, as opposed to the N structures or an accurate frame model required by existing algorithms. The algorithm utilizes the full 3D information in the frame as well as a least squares weighting scheme to achieve highly accurate registration. We use simulated CT data to assess the accuracy of our algorithm. We compare the performance of the proposed algorithm to two commonly used algorithms. Simulation results show that the proposed algorithm is comparable to the best existing techniques with knowledge of the exact mathematical frame model. For CT data corrupted with an unknown in-plane rotation or translation, the proposed technique is also comparable to the best existing techniques. However, in situations where there is a discrepancy of more than 2 mm (0.7% of the frame dimension) between the frame and the mathematical model, the proposed technique is significantly better (p < or = 0.05) than the existing techniques. The proposed algorithm can be applied to any existing frame without modification. It provides better registration accuracy and is robust against model mis-match. It allows greater flexibility on the frame structure. Lastly, it reduces the frame construction cost as adherence to a concise model is not required.