Purpose To dosimetrically evaluate the effects of improper patient positioning in the junction area of a VMAT cranio-spinal axis irradiation technique consisting of one superior and one inferior arc and propose a solution to minimize these patient setup errors. Methods Five (n = 5) cranio-spinal axis irradiation patients were planned with 2 arcs: one superior and one inferior. In order to mimic patient setup errors, the plans were recalculated with the inferior isocenter shifted by: 1, 2, 5, and 10 mm superiorly, and 1, 2, 5, and 10 mm inferiorly. The plans were then compared with the corresponding original, non-shifted arc plans on the grounds of target metrics such as conformity number and homogeneity index, as well as several normal tissue dose descriptors. “Gradient-optimized” plans were then created for each patient in an effort to reduce dose discrepancies due to setup errors. Results Percent differences were calculated in order to compare each of the eight shifted plans with the original non-shifted arc plan, which corresponds to the ideal patient setup. The conformity number was on average lower by 0.9%, 2.7%, 5.8%, and 9.1% for the 1, 2, 5, and 10 mm inferiorly-shifted plans and 0.4%, 0.8%, 2.8%, and 6.0% for the respective superiorly-shifted plans. The homogeneity indices were, averaged among the five patients and they indicated less homogeneous dose distributions by 0.03%, 0.3%, 1.0%, and 2.8% for the inferior shifts and 0.2%, 1.2%, 6.3%, and 15.3% for the superior shifts. Overall, the mean doses to the organs at risk deviate by less than 2% for the 1, 2, and 5 mm shifted plans. The 10 mm shifted plans, however, showed average percent differences, over all studied organs, from the original plan of up to 5.6%. Using “gradient-optimized” plans, the average dose differences were reduced by 0.2%, 0.5%, 1.2%, and 2.1% for 1, 2, 5, and 10 mm shifts, respectively compared to the originally optimized plans, and the maximum dose differences were reduced by 11.7%, 8.5%, 12.4%, and 13.9% on average for the 1, 2, 5, and 10 mm shifted plans. Conclusions Setup errors related to isocenter shifting should be minimized in order to provide the patient with the most dosimetrically accurate treatment possible. Errors of 1–2 mm can negatively affect the quality of the delivered treatment, most notably in the arc junction area, but the deterioration of the treatment plan accuracy is not as problematic as in the cases of larger errors such as 5–10 mm. By employing a new planning technique, the dose differences due to setup errors can be greatly reduced.