BACKGROUND AND PURPOSE: A technique has been previously reported to estimate high-quality 4D-CBCT using prior information and limited-angle projections. This study is to investigate its clinical feasibility through both phantom and patient studies. MATERIALS AND METHODS: The new technique used to estimate 4D-CBCT is called MMFD-NCC. It is based on the previously reported motion modeling and free-form deformation (MMFD) method, with the introduction of normalized-cross-correlation (NCC) as a new similarity metric. The clinical feasibility of this technique was evaluated by assessing the accuracy of estimated anatomical structures in comparison to those in the 'ground-truth' reference 4D-CBCTs, using data obtained from a physical phantom and three lung cancer patients. Both volume percentage error (VPE) and center-of-mass error (COME) of the estimated tumor volume were used as the evaluation metrics. RESULTS: The average VPE/COME of the tumor in the prior image was 257.1%/10.1 mm for the phantom study and 55.6%/3.8 mm for the patient study. Using only orthogonal-view 30° projections, the MMFD-NCC has reduced the corresponding values to 7.7%/1.2 mm and 9.6%/1.1 mm, respectively. CONCLUSION: The MMFD-NCC technique is able to estimate 4D-CBCT images with geometrical accuracy of the tumor within 10% VPE and 2 mm COME, which can be used to improve the localization accuracy of radiotherapy.