To demonstrate the feasibility of performing dose calculation on megavoltage cone-beam CT (MVCBCT) of head-and-neck patients in order to track the dosimetric errors produced by anatomic changes.A simple geometric model was developed using a head-size water cylinder to correct an observed cupping artifact occurring with MVCBCT. The uniformity-corrected MVCBCT was calibrated for physical density. Beam arrangements and weights from the initial treatment plans defined using the conventional CT were applied to the MVCBCT image, and the dose distribution was recalculated. The dosimetric inaccuracies caused by the cupping artifact were evaluated on the water phantom images. An ideal test patient with no observable anatomic changes and a patient imaged with both CT and MVCBCT before and after considerable weight loss were used to clinically validate MVCBCT for dose calculation and to determine the dosimetric impact of large anatomic changes.The nonuniformity of a head-size water phantom ( approximately 30%) causes a dosimetric error of less than 5%. The uniformity correction method developed greatly reduces the cupping artifact, resulting in dosimetric inaccuracies of less than 1%. For the clinical cases, the agreement between the dose distributions calculated using MVCBCT and CT was better than 3% and 3 mm where all tissue was encompassed within the MVCBCT. Dose-volume histograms from the dose calculations on CT and MVCBCT were in excellent agreement.MVCBCT can be used to estimate the dosimetric impact of changing anatomy on several structures in the head-and-neck region.