Wide-angle digital breast tomosynthesis (DBT) gives better depth resolution and tissue separation while the microcalcification (MC) detectability is impacted by many factors, such as detector performance, focal spot motion (FSM), increased noise due to scatter radiation, angular dose distribution and image reconstruction methods. This study aims at developing an in-silico experimental pipeline to compare these factors’ influence on the MC detectability, so that new system design can be proposed to improve the performance. The VICTRE tool developed by Food and Drug Administration was used to generate a 49 mm-thick anthropomorphic digital breast phantom and the projection images using Monte Carlo simulation. We inserted 38 MC clusters with size of 120 μm at 40 mm from the bottom of the phantom. The Monte Carlo simulation used parameters of a clinical wide-angle DBT system, with 25 projections over 50-degree angular range, and 28 kVp W/Rh energy spectrum. Projection images were simulated under different scenarios: uniform/nonuniform angular dose distribution, with/without FSM of 2 mm, with/without scatter radiation, and TFT/CMOS detector types. A four-alternative forced choice (4AFC) methodology was employed to evaluate the MC detectability. The percentage correct and visibility score under all scenarios were compared. The results show that MC detectability decreases with the presence of either increased noise due to scattered radiation, or image blur due to FSM. Nonuniform angular dose distribution improves the detectability of MCs when using FBP reconstruction with narrow slice thickness filter. MC sharpness is improved with CMOS detector with smaller pixel size and lower electronic noise.