Our purpose was to investigate optimal tube voltages (kVp) for a newly developed digital breast tomosynthesis (DBT) process and to determine tube current–exposure time products (mAs) for the average glandular dose (AGD), which is similar to that of the two views in conventional mammography (CM). In addition, the optimal acquisition parameters for this system were compared with those of CM. The analysis was based on the contrast-to-noise ratio (CNR) from the simulated micro-calcifications on homogeneous phantoms, and the figure of merit (FOM) was retrieved from the CNR and AGD at X-ray tube voltages ranging from 24 to 40kVp at intervals of 2kV. The optimal kVp increased more than 2kV with increasing glandularity for thicker (≥50mm) breast phantoms. The optimal kVp for DBT was found to be 4–7kV higher than that calculated for CM with breast phantoms thicker than 50mm. This is likely due to the greater effect of noise and dose reduction by kVp increment when using the lower dose per projection in DBT. It is important to determine optimum acquisition conditions for a maximally effective DBT system. The results of our study provide useful information to further improve DBT for high quality imaging.