Digital tomosynthesis of the breast continues to be intensively studied as an adjunct or replacement of conventional mammography. Although many of the acquisition parameters found in tomosynthesis imaging are also found in conventional mammography and therefore most of the traditional values from mammography have been used in the former, two acquisition geometry parameters, the angular range covered during acquisition and the number of projections per projection set, are applicable only to tomosynthesis. Therefore, in the preclinical and clinical studies reported on tomosynthesis of the breast, a wide variety of values have been used for these two parameters. In this study, 63 different combinations of angular range and number of projections were evaluated using computer simulation methods to characterize how these two parameters affect reconstruction quality and to find which of these combinations maximize it. For this, a computer simulation of a digital tomosynthesis system that included empirically determined system response characteristics was developed and used to generate 9450 different breast tissue volume reconstructions. These reconstructions were analyzed objectively using metrics for in-plane lesion visibility and vertical resolution in the form of the contrast-to-noise ratio and artifact spread function (ASF). It was found that although maximizing the angular range covered does always increase the vertical resolution in tomosynthesis, increasing the number of projections in the acquisition set beyond a relatively low threshold does not further improve the vertical resolution. This threshold value for the minimal number of projections needed to minimize the ASF was found to vary proportionally with angular range. For example, for a 60° angular range, the threshold number of projections was found to be 13. Given the clear inverse relationship between the number of projections and in-plane reconstruction quality under a limited total glandular dose condition, the optimum acquisition geometry in tomosynthesis imaging of the breast is that which maximizes the angular range while maintaining the number of projections close to the threshold values found. Finally, of the 63 acquisition geometries studied, the one that resulted in the highest quality reconstruction, considering both in-plane quality and vertical resolution, consisted of the acquisition of 13 projections over a 60° angular range.